Bronchial artery embolization

Bronchial artery embolization is a treatment for hemoptysis, abbreviated as BAE. It is a kind of catheter intervention to control hemoptysis (airway bleeding) by embolizing the bronchial artery, which is a bleeding source. Embolic agents are particulate embolic material such as gelatin sponge or polyvinyl alcohol (PVA), and liquid embolic material such as NBCA, or metallic coils.

Basic principle
It is said that hemoptysis is caused by the formation of anomalous anastomosis (bronchial artery-pulmonary artery shunt) between the bronchial artery and the pulmonary artery, and if the bronchial artery is embolized, hemorrhage will cease. This is a fundamental concept of BAE. Traditionally, BAE was mostly performed as an emergency hemostatic procedure. Recently, it is often performed as an elective catheter treatment to prevent recurrence after massive hemoptysis, or control chronic repetitive hemoptysis. Although it is termed bronchial artery embolization, various systemic arteries other than the bronchial artery (non-bronchial arteries) also form a shunt with the pulmonary artery and cause hemoptysis. Therefore, it is common to embolize such non-bronchial arteries, but the expression of bronchial artery embolization, BAE, rather than the universal expression "arterial embolization" is more common. The therapeutic outcomes are improving, due to the combined approach such as spreading the treatment target to non-bronchial arteries, development of 3D-CT angiography following the development of MDCT, the advancement of devices such as coils and micro-catheters, and the evolution of therapeutic strategies. BAE has become the gold standard for hemoptysis for its dramatic improvement. Although the hemostatic effect is greatly affected by the underlying disease, some high-volume centers report a hemostatic rate of about 90.4% within one year of treatment, and 85.9% even in two years after treatment. The occlusion of the blood vessels in the brain, heart, and kidneys, which are supplied by the end arteries, can cause cerebral, myocardial, and renal infarctions. In BAE, both bronchial mucosal necrosis and pulmonary infarction seldom occur. It is presumed that this is because the pulmonary circulation is dually controlled by the bronchial artery and the pulmonary artery; and even if the blood flow in the bronchial artery is lost, blood flow from the pulmonary artery is slightly maintained. With non-bronchial arteries, it is empirically known that some collateral circulations also develop. In addition, direct hemorrhage from the pulmonary artery is rare (less than 5%), which requires embolization of the pulmonary artery.

Treatment indications
BAE is effective for hemoptysis in most underlying diseases such as bronchiectasis, nontuberculous mycobacterial disease (NTM), cryptogenic hemoptysis, pulmonary aspergillosis, and pulmonary tuberculosis sequelae. According to Ishikawa who reported long-term treatment results of BAE for 489 hemoptysis patients, each underlying disease's ratio is 34.0%, 23.5%, 18.4%, 13.3%, 6.8%, respectively. Other diseases for which BAE is effective include lung abscess and pulmonary actinomycosis.

As for lung cancer, hemoptysis is caused mostly by bleeding from the tumor itself, and not by the bronchial-pulmonary artery shunt mechanism; embolism of the feeding vessels for the tumor causes necrosis of the cancer which may evoke massive hemoptysis. In addition, subsequent chemotherapy and endovascular treatment cannot be performed if the route of anticancer drugs is permanently obstructed. Lung cancer needs a different strategy. Seki et al. reported the usefulness of endovascular treatment for lung cancer hemoptysis. Kichang et al. reported BAE for hemoptysis in 84 lung cancer patients, and demonstrated that massive hemoptysis and cavity formation were significantly poor prognosis factors; re-hemoptysis rate was 23.8% in their follow-up period.

Even though BAE is currently considered the gold standard treatment for hemoptysis, Ishikawa et al. found that only 9065 patients (8.4%) out of 107,389 patients hospitalized for hemoptysis between 2010 and 2018 in Japan were treated with BAE. According to Ishikawa basically, all patients with hemoptysis who are admitted to the hospital are eligible for BAE, and the reason why BAE has been performed only in such a small number of patients is that there are still few facilities that can perform BAE,

Besides, among the 660 hospitals that performed BAE, half of them (334 centers) experienced less than one case per year. Centralization of hemoptysis treatment facilities will be necessary to increase the performance rate of BAE and to improve the quality of BAE.

Treatment technique details
A catheter with a diameter of less than 2 mm is inserted at the base of the foot (femoral artery) or the artery in the wrist (radial artery). The tip of the catheter is inserted into the orifice of the bronchial artery (normally smaller than 1 mm) or other non-bronchial hemoptysis-related arteries. Contrast agent is injected through the catheter, and when abnormal findings are observed, such as systemic–pulmonary shunts, proliferations of the capillary vessels, or extravasation of the contrast medium to the lung tissues, they were super selectively embolized using the 3 Fr microcatheter system. A thinner microcatheter (about 0.8 mm) is passed through the catheter into the blood vessel, and then, embolic material is injected into the appropriate site. Thus, hemostasis is performed by ceasing or reducing the pressure applied to a bronchial (or non-bronchial)-pulmonary shunt (abnormal anastomosis). BAE is performed under local anesthesia, and the required time is about 1 hour to 3 hours.

Effectiveness
In the past, BAE was mostly considered a palliative or a bridge therapy to surgical operation owing to the high rate of re-hemoptysis with BAE. But with the improvement in treatment strategy and devices, it is regarded as a permanent therapy for hemoptysis nowadays.

There are few facilities in which sophisticated BAE is feasible, and there are significant disparities between hospitals in the treatment quality and their experience. In most of the facilities, BAE is operated by interventional vascular radiology doctors, but in recent years, specialized high volume centers where a trained pulmonologist performs BAE are emerging. It is particularly effective for cryptogenic hemoptysis. Ando, Masuda et al. reported in their article that the hemostatic rate is 97% at 20 months, which is equivalent to the results of the article by Ishikawa. Ando, Masuda et al. state that micro bronchial aneurysms are involved in 22.9% of cryptogenic hemoptysis

For pulmonary aspergillosis, BAE was relatively less effective and was once thought to be contraindicated, but hemostatic rates have improved in recent years. Ando, Masuda et al. demonstrated that the re-hemoptysis rate was significantly higher in cases of disease progression.

The hemostatic rate in each underlying disease by Ishikawa is shown below. In this paper, both re-hemoptysis and death are defined as composite endpoints, and among these, only re-hemoptysis free rate is shown in the following table. It is originally a long-term performance data for 3 years; In the third year, the 95% confidence interval was too wide except for cryptogenic hemoptysis; hence, they are regarded as statistically unreliable figures. Therefore, the third year result is not posted here except for idiopathic hemoptysis. The poorest hemostatic rate after 2 years was observed in nontuberculous mycobacterial disease (NTM). The result shown by Okuda, Masuda et al. was similar (73.8%). It is considered to reflect the progressive nature of the disease.

Below are the treatment results summarized according to underlying diseases based on peer-reviewed papers published by Eishinkai Kishiwada Rehabilitation Hospital Hemoptysis and Pulmonary Circulation Center (EHPC), and The National Hospital Organization Tokyo Hospital Pulmonary Circulation and Hemoptysis Center (Tokyo Hp) ; the top two representatives of high-volume centers in Japan.

In cases of recurrence, re-BAE is possible to perform several times.

Furthermore, Takeda et al. showed that the 1, 2, 3, and 5-year hemostatic rates of bronchiectasis (without nontuberculous mycobacteriosis or pulmonary aspergillosis) were 91.3, 84.2, 81.5, and 78.9%, respectively. This paper is valuable for its long-term results of 5 years.

Embolic material
These include polyvinyl alcohol (PVA), n-butyl-2-cyanoacrylate (NBCA), gelatin sponge, metallic coil, etc.

PVA - Woo et al. reported 406 cases of BAE long-term results, including 293 cases of PVA and 113 cases of NBCA.

NBCA - This is a kind of medical instant adhesive. Generally, there are many complications such as non-target blood vessel embolization and adhesion of catheter and vessel wall. However, in the article by Woo et al., major complication rate was 0%.

This kind has many advantages, such as low cost, instantaneous embolization, and very low recanalization rate since it does not depend on the patient's thrombus formation. It appears to be the best indication for traumatic bleeding control, particularly, in the peripheral bronchial aneurysms that the micro-catheter cannot access in BAE procedures, is a very good indication, and Mine, Hasebe et al. reported a technique called B-glue; NBCA combined with a balloon.

Gelatin sponge (GS)
Gelatin sponge (GS) is a transient embolic material, and in most cases, it dissolves within one to two weeks, and blood flow resumes. For this reason, it is important for emergency hemostatic purposes such as palliative treatment until surgery, which was the former positioning of BAE. GS is not suitable for the prevention of recurrence after massive hemoptysis or elective BAE for chronic repetitive hemoptysis. Wada et al. demonstrated that hemostatic rate was 24% (median follow-up time was 15 months) in their retrospective analysis of BAE for 33 patients using GS.

Metallic coil
There are three kinds of platinum vascular embolic coil. One is a detachable coil, which is expensive, but can be deployed repetitively until electric detach. This enables safest and fully controlled embolization. The second one is pushable coil, which is affordable, and allows for only one deployment. The third one is mechanical detachable coil; it has a moderate price range, and repetitive deployment is feasible. Ishikawa termed BAE with metallic coil as ssBACE, and published the world's largest number of cases of ssBACE long-term results in 2017. As described below, there are no reports on spinal cord ischemia in ssBACE, which is considered the most serious complication of BAE. This is one of the strongest merit of ssBACE.

Despite a rumor that it cannot be re-treated if ssBACE is performed once, Ryuge demonstrated in their article on "the mechanism of re-hemoptysis" that the technical success rate in re-BAE was at least 97.7%.

Re-hemoptysis mechanism
Ryuge classified the re-hemoptysis mechanism after ssBACE into four as shown below. They also demonstrated that for the improvement of the long-term results in ssBACE in the future, suppressing recanalization is necessary.

Some readers misunderstand that 45.2% of the embolized coils recanalized. This, in fact, is the ratio of re-hemoptysis mechanism occurring in 9.6% cases in 1 year, and in 14.1% of those in 2 years.

Recanalization was the main cause of re-hemoptysis, and the suppression of new hemoptysis-related vessels, which is the second cause, cannot be controlled by the BAE procedure itself. It was shown that suppression of the recanalization was the key to improvement in ssBACE result in future.

Complications
Chest pain is the most common complication for who had undergone BAE, ranging from 24 to 91%. However, the symptom is temporary due to accidental embolisation of coronary artery supplying the heart. In the past, paraplegia caused by spinal cord ischemia due to erroneous embolization of the anterior spinal artery was well known as a rare, but serious complication. Super selective BAE using microcatheter reduced the incidence of the spinal ischemia.

However, according to Ishikawa et al., spinal cord infarction still occurs, with an incidence of 0.19% (16/8563).

They also compared it between three embolic agents (GS, NBCA, Coil) and demonstrated that the incidence of spinal cord infarction was significantly lower in coils: 0.06% (1/1577) compared with GS 0.18% (12/6561) and NBCA 0.71% (3/425) (p=0,04).

Major complications reported by Ishikawa et al. are presented below.

Mediastinal hematoma occurs by injury of hemoptysis-related vessel, mainly by wire, and can easily bail out by proximal coil embolization.

Improvement in mortality and quality of life
The majority of research on BAE was the single-center retrospective observational studies. Descriptive epidemiological studies using French medical big data is precious in that aspect. From the fall of 2020 to January 2021, a collaborative study led by the Yasunaga Laboratory of the University of Tokyo published two landmark papers using the Japanese medical database. One of them is a study by Ando et al. of the Department of Respiratory Medicine, University of Tokyo, which demonstrated for the first time in the world that early BAE (within three days after endotracheal intubation) significantly reduced in-hospital mortality in patients with severe hemoptysis on ventilators (30 days): 7.5% in the early BAE group vs. 16.8% in the non-early BAE group. (odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001).

Omachi et al. of the Hemoptysis and Pulmonary Circulation Center, Kishiwada Rehabilitation Hospital, demonstrated for the first time in the world that elective BAE with coils significantly improved the quality of life of hemoptysis patients(single-center prospective observational study). In this study, both physical and mental QOL improved significantly after BAE, especially the latter.

Main evidence for BAE

 * 1) Bronchial artery embolization to control hemoptysis: comparison of N-butyl-2-cyanoacrylate and polyvinyl alcohol particles  An important paper with long-term results from Seoul National University encompassing 406 cases (293 PVA cases, 113 NBCA cases). The non-hemoptysis survival rates at 1, 3, and 5 years for PVA were 77%, 68%, and 66% respectively, and 88%, 85%, and 83% for NBCA, higher in the NBCA group (P = .01). NBCA was associated with fewer complications and better outcomes than previously reported for PVA.  Woo S, Yoon CJ, Chung JW, et al. Radiology. 2013 Nov;269(2):594-602. PMID 23801773.
 * 2) Haemoptysis in adults: a 5-year study using the French nationwide hospital administrative database  An epidemiological study on hemoptysis using the French insurance healthcare database (2008-2012). Approximately 15,000 hospital admissions for hemoptysis occur annually, making up 0.2% of all admissions. 50% of hemoptysis causes were idiopathic, followed by respiratory infections (22%), lung cancer (17.4%), bronchiectasis (6.8%), pulmonary edema (4.2%), anticoagulants (3.5%), tuberculosis (2.7%), pulmonary embolism (2.6%), and aspergillosis (1.1%). Mortality rates were 9.2% during the initial admission, 21.6% at 1 year, and 27% at 3 years.  Abdulmalak C, Cottenet J, Beltramo G, et al. Eur Respir J. 2015 Aug;46(2):503-11. PMID 26022949.
 * 3) Bronchial artery embolization in hemoptysis: a systematic review  The first systematic review for BAE, covering papers from 1976 to 2016, including 22 studies with at least 50 cases each. Recurrence rates for BAE were found to be high, between 10% to 57%. The presence of non-bronchial systemic arteries, bronchopulmonary shunts, aspergillosis, recurrent tuberculosis, and multi-drug resistant TB significantly increased the risk of recurrence (P < 0.05). The complication rate was nearly 0.1% (0%-6.6%). Despite high recurrence rates, BAE remains the preferred intervention in emergencies, for surgically unfit patients, or those with extensive or bilateral lung disease.  Panda A, Bhalla AS, Goyal A. Diagn Interv Radiol. 2017 Jul-Aug;23(4):307-317. PMID 28703105.
 * 4) Efficacy and Safety of Super Selective Bronchial Artery Coil Embolization: A Single-Center Retrospective Observational Study  This study evaluated the safety and long-term outcomes of ssBACE for treating hemoptysis. It included 489 patients from a single-center retrospective study, excluding those with malignancies or on dialysis. The technique showed high success rates (93.4%) and 2-year hemoptysis-free survival rates comparable to NBCA and PVA. Major complications were few, demonstrating its safety.  Ishikawa H, Hara M, Ryuge M, et al. BMJ Open. 2017 Feb 17;7(2):e014805. PMID 28213604.
 * 5) Mechanisms of Recurrent Haemoptysis after Super-Selective Bronchial Artery Coil Embolisation  The study dissected the mechanisms of recurrent hemoptysis after ssBACE into four categories: recanalization of embolization, new vessel emergence, collateral from the same vessel, and collateral from other vessels. Recanalization was the most frequent cause, followed by new vessel growth. The findings suggested that reducing recanalization is crucial for improving treatment outcomes.  Ryuge M, Hara M, Hiroe T, et al. Eur Radiol. 2019 Feb;29(2):707-715. PMID 30054792.
 * 6) Effect of tranexamic acid on mortality in patients with haemoptysis: a nationwide study  This epidemiological study utilized Japan's DPC healthcare database. Among 28,539 hospital admissions for hemoptysis, 17,049 were administered tranexamic acid, and 11,490 were not. Propensity score matching yielded 9,933 matched pairs, showing significantly lower in-hospital mortality in the tranexamic acid group.  Kinoshita T, Ohbe H, Matsui H, et al. Crit Care. 2019 Nov 6;23(1):347. PMID 31694697.
 * 7) Erratic Coil Migration in the Bronchus after Bronchial Artery Embolization  The study reported two cases of coil migration from the bronchial artery to the bronchus after ssBACE. Although no recurrence of hemoptysis was observed, one case required coil retrieval. The retrieval strategy and underlying mechanistic hypothesis were proposed.  Ishikawa H, Omachi N, Ryuge M, et al. Respirol Case Rep. 2019 Aug 22;7(8):e00478. PMID 31463064.
 * 8) Early Arterial Embolization and Mortality in Mechanically Ventilated Patients With Hemoptysis: A Nationwide Retrospective Cohort Study - Another epidemiological study using Japan's DPC database. It compared patients who received BAE within 3 days of intubation (early embolization group) to those who did not (control group), showing lower mortality rates and shorter duration of mechanical ventilation in the early embolization group.  Ando T, Kawashima M, Jo T, et al. Crit Care Med. 2020 Oct;48(10):1480-1486. PMID 32931191.
 * 9) Spinal Cord Infarction after Bronchial Artery Embolization for Hemoptysis: A Nationwide Observational Study in Japan - This study used Japan's DPC healthcare database to determine the incidence of spinal cord infarction after BAE, revealing a rate of 0.19%. The incidence varied depending on the embolic material, with significantly lower rates for coils.  Ishikawa H, Ohbe H, Omachi N, et al. Radiology. 2021 Mar;298(3):673-679. PMID 33464182.
 * 10) The Impact of Bronchial Artery Embolization on the Quality of Life of Patients with Haemoptysis: A Prospective Observational Study - The study quantitatively demonstrated the mental anguish of patients with hemoptysis and the relief provided by BAE, indicating an improvement in both physical and particularly mental QOL after BAE.  Omachi N, Ishikawa H, Hara M, et al. Eur Radiol. 2021 Jul;31(7):5351-5360. PMID 33409794
 * 11) High false-negative rate of the anterior spinal artery by intercostobronchial trunk arteriography alone compared to CT during arteriography - The study examined the false-negative rate of identifying the anterior spinal artery during regular arteriography compared to when using IVR-CT during BAE, finding a 71% rate of missed detections (false negatives). It also found that the anterior spinal artery was not identified from the bronchial artery, only from the intercostal artery and ICBT (intercostal artery common trunk).  Kodama Y, Sakurai Y, Yamasaki K, et al. Br J Radiol. 2021 Jul 1;94(1123):20210402. PMID 34111972.
 * 12) Bronchial Artery Aneurysm: Prevalence, Clinical Characteristics, and Long-Term Prognosis Following Bronchial Artery Embolization - This study is the first original research article on BAA, previously only reported in case reports, investigating the prevalence, characteristics, and long-term prognosis of BAA in BAE cases, showing a prevalence of 3.9% (20/508).  Omachi N, Ishikawa H, Nishihara T, et al. J Vasc Interv Radiol. 2022 Feb;33(2):121-129. PMID 34752932.
 * 13) CIRSE Standards of Practice on Bronchial Artery Embolisation - The world's first BAE guidelines by CIRSE, marking a paradigm shift from emergency BAE for massive hemoptysis in fear of spinal cord infarction to a safer elective BAE for chronic recurrent hemoptysis.  Kettenbach J, Ittrich H, Gaubert JY, et al. Cardiovasc Intervent Radiol. 2022 Jun;45(6):721-732. PMID 35396612.
 * 14) Prevalence of Non-Bronchial Systemic Culprit Arteries in Patients with Hemoptysis with Bronchiectasis and Chronic Pulmonary Infection Who Underwent De Novo Bronchial Artery Embolization - The study described the relationship between bleeding sites (pulmonary lobes) and targeted non-bronchial systemic arteries in patients with hemoptysis due to bronchiectasis and chronic pulmonary infection. Non-bronchial systemic arteries accounted for 66% of the targeted vessels, with the internal thoracic artery, intercostal artery, and inferior phrenic artery being the most frequent.  Nishihara T, Ishikawa H, Omachi N. Eur Radiol. 2023 Jun;33(6):4198-4204. PMID 36472693.
 * 15) A Technical Manual of Bronchial Artery Embolization by Coil for Pulmonologists: An Expert's Opinion - A review article summarizing BAE techniques, especially ssBACE techniques, for pulmonologists aspiring to perform BAE, including general discussions on major classifications and severity of hemoptysis in the first part.  Ishikawa H, Yamaguchi Y, Nishihara T, et al. Respir Endosc. 2023;1(2):28-41. https://doi.org/10.58585/respend.2023-0035