Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Returning home now from Japan

Last Updated: April 03, 2024

Disclosure: IML has relationships with drug companies including AOP-Health, Actelion-J&J, MSD, United Therapeutics, MSD, Neutrolis, Pulnovo and Ferrer. In addition to being investigator in trials involving these companies, relationships include consultancy service, research grants, and membership of scientific advisory boards.
Pub Date: Thursday, Mar 07, 2024
Author: Irene M. Lang M.D.
Affiliation: Department of Internal Medicine II, Division of Cardiology, Center of Cardiovascular Medicine, Medical University of Vienna, Austria

View the summary for Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension

The American Heart Association should be commended for the initiative to address Balloon Pulmonary Angioplasty (BPA), an emerging percutaneous cardiovascular intervention targeting major vessel lesions of chronic thromboembolic pulmonary hypertension (CTEPH) in a scientific statement. The pulmonary vascular bed has not been in the mainstream of cardiology, but awareness is now raised through this article. The focus is well deserved because BPA is historically based in the US with the first larger series published in 2001 by Feinstein and colleagues 1 who described 18 patients with CTEPH who underwent BPA. However, lung injury occurred in 11 patients and 30-day mortality was 5.5%. Because of these outcomes the procedure was criticized and abandoned at the time. Since the refinement by Japanese interventionists in 2012 2, BPA has returned to Europe and the US and has been practiced in >7,000 documented patients 3.

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The AHA scientific statement entitled Current Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thrombo-Embolic Pulmonary Disease with and without Pulmonary Hypertension is timely, and authors have tried to summarize the current status of the procedure and to provide a consensus opinion on the role of BPA in the care of patients with CTEPH. Authors under the leadership of Vikas Aggarwal also attempted to provide guidance for new BPA programs, and identify unmet needs. Achieving consensus in the logistic, strategic and technical requirements for BPA will guarantee optimized delivery of care for CTEPH patients involving cardiologists, with the goal to achieve cure in partnership with pneumology, radiology and thoracic surgery.

What is CTEPD, and what is CTEPH?

CTEPH is a long-term complication of pulmonary embolism (PE) with a cumulative incidence reaching 2.3% within the first two years after symptomatic PE 4, and an estimated prevalence in Europe of approximately 50/Million. CTEPH is underdiagnosed in the population, and more awareness will tease out cases from other diagnostic groups like heart failure, chronic obstructive pulmonary disease and valvular heart disease.

According to the most recent classification 5, the overarching term Chronic Thromboembolic Pulmonary Disease (CTEPD) has been introduced, creating some confusion. If mean pulmonary artery pressure (mPAP) is >20mmHg mmHg, PVR >2 Wood Units and chronic/organized flow-limiting thrombi/emboli exist in the elastic pulmonary arteries (main, lobar, segmental, subsegmental) after at least three months of effective anticoagulation, a diagnosis of CTEPD with PH is made, corresponding to CTEPH. Roughly 3% of patients with CTEPD may present with mean pulmonary artery pressure (mPAP) <25mmHg at rest despite symptoms, and those are labeled as CTEPD without PH (previous CTED). However, one may speculate that this condition might in the future be even less common when the new definition of PH, including the definition for exercise PH will be generally applied 5. Therefore, the term CTEPH will be mainly used and should continue to be used.

Who can do BPA, and for whom?

BPA is performed by those trained in percutaneous balloon techniques (interventional cardiologists or radiologists), and equipped with basic knowledge about pulmonary vascular anatomy and physiology. However, the most important requirement for a BPA program is the embedding in a mutlidisciplinary CTEPH team including PEA surgeons, BPA interventionalists, cardiologists, pulmonologists, imagers, and nurses. BPA is performed as stand-alone procedure, simultaneous with PEA 6, in sequence with PEA 7, and in combination with PEA and medical treatments 8, 9. In the current treatment paradigm BPA is performed in patients who are technically inoperable, mainly because of distal lesions at the segmental and subsegmental level, or not surgical candidates due to medical co-morbidities, or not willing to undergo PEA, or inoperable for logistical reasons.

How is BPA done, and what are procedural complications?

BPA is a classical percutaneous transcatheter technique 10 that is performed stepwise, one lung at a time, in usually 4-6 subsequent sessions. While injury of the medial layer is a principle of coronary intervention, BPA addresses intraluminal obstruction without medial dissection, and without restenosis. Mechanisms of lumen enlargement are vessel stretching immediately after BPA 11, and continuous vessel enlargement, presumably due to a process of flow-mediated dilatation over several months 12 13 .

Biplane angiography enhances anatomic resolution and is of great value to safe BPA. Guide extensions and direct injection allow for precise lesion discrimination. MPAP >40 mm Hg and/or pulmonary vascular resistance ≥ 7 Wood units 14, 15 signify higher risk for vascular injury and require 2.0 or 2.5 mm balloons, particularly in the first sessions. The main complication of BPA is lung injury (LI) due to the wire or balloon which occurred in 6.4% of sessions in the Polish multicenter registry 16, in 9.1% of sessions in the French Registry 15 and in 9.4% of sessions in the Bad Nauheim report 17, resulting in hemoptysis, pulmonary opacifications, and hypoxemia and shock. All reported series have documented that complications decrease with learning. For example, in France severe lung injury was reduced from 20% to 4% per patient 15. The recent European Consensus Statement on BPA 3 is offering a classification for complications, intended to facilitate reporting in future BPA trials that should include reporting per session and per patient. BPA safety has been significantly improved over the years, with decreasing periprocedural mortality, recently reported as 0.2% 18.

Does BPA work?

The AHA statement delivers a large data table. BPA is an effective treatment, resulting in an average decrease of mPAP by 33%, and PVR by at least 50% from baseline 19, which is greater than the effect of medical monotherapy alone (mPAP by 7% and PVR by 25% decrease from baseline) 19. In parallel to improved hemodynamics at rest, Quality of life, exercise capacity and WHO functional class improve 20, right ventricular functional improvements are documented by echo and cardiac magnetic resonance 21-24, echocardiographic speckle tracking analysis 25, and phase-contrast magnetic resonance imaging 26.

What are open issues?

Remaining questions are: Is complete BPA hemodynamic normalization, restoration of right ventricular function, a mPAP/CO slope of >3 mmHg/L/min during exercise, or improved quality of life? What is the best initial mechanical treatment, PEA or BPA 27? Should all patients undergoing BPA be pre-treated with drugs approved for CTEPH? More insights are expected from the results of the International BPA Registry (NCT03245268).

What are the key messages of the AHA statement?

The must-knows for a BPA-cardiologist:

  1. You cannot do BPA in isolation, you need a CTEPH team
  2. You need to know pulmonary vascular anatomy and variation
  3. You should have access to biplane angiography
  4. You need to engage all pulmonary artery segments selectively with a guiding catheter
  5. You need to have done about 100 BPAs to be qualified to work alone, and your center needs to have completed a learning curve with about 100 patients.
  6. You need to recognize vascular injury, and be able to manage it acutely
  7. BPA mortality should be <2% in your center

Conclusions

The American Heart Association has adopted BPA as a component of cardiovascular care.

CTEPH is a relatively common and excellently treatable form of pulmonary hypertension that should not be misdiagnosed or overlooked.

While PEA provides a cure for patients with operable disease, BPA has become a successful treatment for patients with not-operated disease, whichever are the definitions of operability. Results from BPA are more often reported in combination with drugs approved for CTEPH than results from PEA.

Recent data suggest that the evolving approach to CTEPH treatment will be multimodal combining PEA, BPA and medical therapy, which necessitates that BPA is performed in the context of a CTEPH team.

Data from a most recent CTEPH European registry (run 2015 and 2016) demonstrate that PEA, BPA and medical therapy have contributed to significantly improved survival of CTEPH patients 15, 28-31 compared with survival in the eighties 32, or with data from the first European CTEPH registry 33.

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Citation

Aggarwal V, Giri J, Visovatti SH, Mahmud E, Matsubara H, Madani M, Rogers F, Gopalan D, Rosenfield K, McLaughlin VV; on behalf of the American Heart Association Council on Clinical Cardiology; Council on Peripheral Vascular Disease; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; and Council on Cardiovascular and Stroke Nursing. Status and future directions for balloon pulmonary angioplasty in chronicthromboembolic pulmonary disease with and without pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. Published online March 7, 2024. doi: 10.1161/CIR.0000000000001197

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