Changing Profiles of Diagnostic and Treatment Options in Subclavian

Eur J Vasc Endovasc Surg (2010) 40,27e34

REVIEW Changing Proﬁles of Diagnostic and Treatment Options in Subclavian Artery Aneurysms

B.P. Vierhout a,*, C.J. Zeebregts b, J.J.A.M. van den Dungen b, M.M.P.J. Reijnen c a Department of Surgery, Wilhelmina Hospital Assen, Assen, The Netherlands b Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, Groningen, The Netherlands c Department of Surgery, Alysis Zorggroep, Location Rijnstate, The Netherlands

Submitted 3 December 2009; accepted 9 March 2010 Available online 15 April 2010

KEYWORDS Abstract Background: Subclavian artery aneurysms (SAAs) are rare and may cause life- and Aneurysm; limb-threatening complications. Therapeutic options greatly differ as do access alternatives. Complications; The aim of the study was to assess its clinical presentation, diagnostics and therapeutic options Conventional; as reported in the literature. Endovascular; Method: A literature search was performed of the Medline, Cochrane and EMBASE databases. Subclavian artery; All articles, published until September 2009, describing treatment of an SAA were included. Treatment Results: A total of 191 reports, of which 126 met the inclusion criteria, were identified and were published from June 1915 until September 2009. Of these, 394 SAAs were described in 381 patients, with a mean age of 52 16 years. The median diameter was 40 mm (range: 10e180 mm). The aetiology appeared to change in time towards more exogenous causes. Fifty- one percent of the SAAs presented with a pulsating mass, shoulder pain and/or non-specific chest pain. Embolisation, rupture and thrombosis were present in 16%, 9% and 6% of patients, respectively, and their incidence was related to the anatomical localisation of the SAA. Open surgery and endovascular repair had a complication rate of 26% and 28%, respectively (p Z 0.49). Cardio- pulmonary complications were restricted to open repair. Mortality rates for open and endovascular techniques were similar (5%). The mortality rates for conventional elective and emergency procedures were 3% and 13%, respectively, and for endovascular repair 4% and 8%, respectively. Conclusion: The profiles of diagnostic and treatment options of SAAs are changing. Although guidelines considering timing of intervention may not be conducted from available literature, intervention appears to be indicated, especially in distal SAAs, due to the risk of thrombo-embolic complications. Endovascular repair and hybrid procedures appear to be the preferred treatment modalities, due to a lower rate of cardiopulmonary complications. ª 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

* Corresponding author. Tel.: þ31 592 325555; fax: þ31 592 325307. E-mail address: [email protected] (B.P. Vierhout).

The incidence of subclavian artery aneurysms (SAAs) has been patients with an aberrant right SAA, 15 reports only repeatedly reported to be rare.1e7 Dent et al. identified only described the existence or incidence of a SAA and one study two SAAs in their series of 1488 aneurysms.8 In that study, was a duplicate publication. The 126 reports included could however, all false, postoperative, dissecting and mycotic be categorised into 10 single-centre series and 116 case aneurysms were excluded. According to Wickham and Martin, reports. Three-hundred and eighty-one patients were only 57 cases had been described until 1963.9 Since then the diagnosed with 394 SAAs. Two-hundred and eleven patients frequency of reports in literature has increased. were described in single-centre series and 170 in case The SA consists of an intra- and an extra-thoracic part, reports. The mean age of patients was 52 16 years, with while anatomically it may be divided into four parts.10 From a maleefemale ratio of 59:41. The median diameter of the a surgical point of view, a more practical categorisation SAA was 40 mm (range: 10e180 mm) and 57% were right- into three parts has been suggested: a proximal, a middle sided. and a distal part.11 The proximal part extends from its origin, the innominate artery on the right and the aorta on Aetiology and localisation the left side, to the medial border of the scalene muscles. The middle portion of the SA is located dorsal to the The aetiology of SAAs has been summarised in Table 1. Until scalene muscles. The distal part of the SA extends from the 1980, most SAAs were related to TOS, infection or athero- lateral border of the anterior scalene muscle to the lateral 12 sclerosis. Afterwards, traumatic and iatrogenic causes were border of the first rib. more frequently described, while atherosclerosis and The aetiology of an SAA in early publications was frequently collagen disorders remained important. of mycotic, syphilitic or tuberculotic origin. In 1916, the The majority (39%) of SAAs were located in the proximal thoracic outlet syndrome (TOS), also called costoclavicular segment of the SA. The middle segment accounted for 25%, compression syndrome, was recognised as an evoking mech- and 24% was located in the distal segment. In the remaining anism of SAA formation.13 Due to limb- or even life- 14 11% of cases, localisation of the SAA was not described. The threatening complications treatment is usually indicated. evoking mechanisms of SAA formation seemed to differ The current study was performed in order to summarise between each region of the SA. Proximal aneurysms were available data on all aspects related to SAA, including mostly caused by atherosclerosis (19%), collagen disorders aetiology, clinical presentation, diagnostics, treatment (18%), trauma (15%), infection (13%) and in-hospital modalities and complications. procedures (12%). The middle segment SAAs were mainly caused by collagen disorders (23%), trauma (15%), in- Materials and methods hospital procedures (10%), infection (10%) and TOS (15%). A distal SAA was mostly described in relation to TOS (46%) or A search was conducted to identify reports in which as a consequence of blunt or penetrating trauma (23%). treatment of a non-anomalous SAA was described, using the MEDLINE, EMBASE and Cochrane databases. Papers were Clinical presentation included from the start of the databases until September 2009. Earlier publications were tracked using manual cross- Fifty-one percent of patients presented with a pulsating referencing with the earliest article published in June 1915. mass, shoulder pain and/or non-specific chest pain. Other The following MeSH search terms were used: aneurysm, symptoms included local compression, embolisation, subclavian artery and therapy. These terms were applied in thrombosis and rupture (Table 2). Brachial plexopathy was various combinations in addition to the use of the ‘related 15e the most frequently described sign of local compression. articles’ function. Full-text articles were studied without 32 Symptoms of local compression were atypical in many restriction of language of publication and manual cross- cases. In this context, compression of the stellate ganglion referencing was performed. Demographic data, aneurysm 18,20,22,30,32e35 induced Horner syndrome or facial anhyd- characteristics, treatment modalities, complication and rosis,18,22,36 while recurrent laryngeal nerve compression survival data were extracted using standardised criteria. e caused hoarseness.7,18,32,34,37 40 Dysphagia and dyspnoea, Included reports had to contain above-mentioned data. due to compression of the oesophagus and trachea, When two or more studies from the same institution were 10,33,34,38,41e46 respectively, have also been reported. identified, the study of larger size or better quality was Subclavian vein compression, causing venous congestion, included, unless the reported outcomes were mutually was described once47 and another report described exclusive. Reports were excluded from further analysis if compression of the mammarian artery after coronary artery they did not clearly describe diagnostics and treatment, or bypass surgery.48 if treatment of an aberrant right subclavian aneurysm Embolisation, often related to TOS, was described in 16% (ARSA) was reported. Reports published before 1980 were (n Z 56) of cases both to the upper extremity (n Z 44) and compared to those published afterwards. This arbitrary cut- the cerebrum (n Z 12). Cerebrovascular accidents were off point at 1980 was chosen since in that decade the first also reported in a patient with fibromuscular dysplasia,4 in reports were published on endovascular repair. 49 a patient 18 months after a motor vehicle accident and in a patient with an atherosclerotic aneurysm.37 Limb-loss due Results to embolisation has never been reported, but embolisation was fatal in one patient.44 A total of 191 reports on SAAs were identified of which 126 Thrombosis occurred in 21, mostly female, patients with met the inclusion criteria. A total of 49 reports presented TOS, in the age range of 17e57 years. These were all true Subclavian Artery Aneurysms 29

Table 1 Aetiology of SAA. Diagnostic tools

Etiology Before 1980 After 1981 Overall Diagnosis of an SAA is strongly related to its symptoms and Number Number Number localisation. SAAs, located in the middle and distal of cases (%) of cases (%) of cases (%) segment, are regularly diagnosed at physical examination Trauma 5 (10%) 123 (37%) 128 (33%) (48% and 59%, respectively). Aneurysms of the proximal Atherosclerosis 12 (24%) 60 (18%) 72 (19%) part of the SA are mostly diagnosed on a routine chest X-ray T.O.S. 12 (24%) 59 (18%) 71 (18%) (41%) and less frequently at physical examination (13%). Iatrogenic 0 (0%) 32 (10%) 32 (8%) A suspicion of an SAA was often conﬁrmed by angio- Collagen disorders 5 (10%) 24 (7%) 29 (7%) graphy, which used to be the gold standard. Nowadays, the Mycotic 8 (16%) 13 (4%) 21 (5%) investigation of choice for initial diagnosis is duplex ultra- 69 Unknown 3 (6%) 4 (1%) 7 (2%) sound scanning. Angiography was performed in 50% of the Coarctation aortae 2 (4%) 5 (1%) 7 (2%) reports before surgical exclusion. Computed tomography Congenital 1 (2%) 4 (1%) 5 (1%) angiography (CTA; 14%) and magnetic resonance angiog- Post-radiotherapy 0 (0%) 5 (1%) 5 (1%) raphy (MRA; 3%) are increasingly being used (Fig. 1). H.I.V. 0 (0%) 3 (1%) 3 (1%) Not deﬁned 3 (6%) 4 (1%) 7 (2%) Treatment modalities

Total 51 336 387 The indication for exclusion of an SAA is usually based on prevention of upper limb thrombosis, embolisation and rupture. The risk of development of these complications aneurysms with a relatively small diameter of 12e may depend on various aneurysm-related characteristics, 25 mm.9,17,50,51 Thrombosis never appeared to have a fatal including its aetiology and localisation. Treatment modali- outcome, but two patients50,51 lost their hand because of ties include conservative management, open surgical gangrenous complications. repair, endovascular exclusion and various hybrid Rupture was reported in 32 patients (9%) and was fatal in techniques. six of them. In another patient, rupture resulted in amputation.52 Most survivors presented with an episode of hae- Conservative management moptysis, which may be considered as an early sign of Conservative management, consisting of best medical e rupture (n Z 9).18,37,38,53 57 A rupture towards superficial treatment and observation, was described in seven e tissues might also facilitate early recognition.35,52,53,58 62 patients. Four patients, having an underlying disease that One SAA, in a patient suffering from syphilis, ruptured withheld them from surgery, eventually died of into a lung.63 Two others, related to aortic coarctation and rupture.39,41,57,63 Three of these patients had a mycotic SAA an aspergilloma, respectively, ruptured into the pleural and one suffered from severe pulmonary insufficiency. The cavity and had a fatal outcome.64,65 Two other patients remaining three patients refused surgery and showed no survived a pleural rupture.66,67 Ten ruptures towards aneurysm growth within a follow-up duration of 1 year.2,6,70 superficial tissues were described in seven cases after The aetiology of the SAA in these patients was associated trauma59,68 and three others after medical interven- with coarctation of the aorta, atherosclerosis and tions.35,53,60 Two SAAs presented with a pulsatile bleeding idiopathic. following cervical sympathectomy58 and radiotherapy,53 respectively. Sixteen percent of patients with a SAA presented without symptoms. Most of them were described in the past decade. They were mainly found unexpectedly during preoperative screening or in a routine chest X-ray following introduction of a central venous catheter.

Table 2 Incidence of reported symptoms of a SAA. Type Symptoms Percentage Local signs Pulsating mass, shoulder pain, 51% non-speciﬁc chest pain Rupture Hemoptysis, hematothorax, 9% open rupture, hemorrhage Compression Dysphagia, dyspnoe, brachial 36% plexopathy, Horner’s syndrome, hoarseness Thrombosis Ischemic arm 6% Embolization Numb or cyanotic ﬁngers, 16% Figure 1 CT-angiography of a 36-year old female patient cerebral infarction with a middle segment SAA related to TOS. Arrow pointing at the SAA. 30 B.P. Vierhout et al.

Conventional surgical repair Table 3 Incidence of complications following SAA repair. Three-hundred and twenty-nine patients underwent conventional surgery. Access options for the proximal SA Open repair Endovascular Hybrid greatly differed and included right and left thoracotomy, Number of Number of Number of sternotomy with and without supraclavicular or trans- cases (%) cases (%) cases (%) clavicular access, axillary access and anterior thoracoto- No complications 239 (73%) 36 (75%) 8 (80%) mies in combination with mini-sternotomy and Early thrombosis 4 (1%) 1 (2%) 1 (10%) supraclavicular access. The middle segment of the SA Late thrombosis 4 (1%) 3 (6%) 0 (0%) appeared usually easier to reach using a supraclavicular Stenosis 0 (0%) 2 (4%) 0 (0%) access. This approach may be combined with an infracla- False aneurysm 0 (0%) 4 (8%) 0 (0%) vicular incision, clavicular division and (partial) clavicular Disintegrating 0 (0%) 2 (4%) 0 (0%) resection. In cases of a SAA due to TOS, aneurysm repair nitinol wire was often combined with first-rib resection.71,72 Abscess 3 (1%) 1 (2%) 0 (0%) Various surgical procedures have been described for the Graft infection 2 (1%) 0 (0%) 0 (0%) exclusion of a SAA. The first described treatment option e e Ischemic arm 6 (2%) 1 (2%) 0 (0%) was ligation only11,18,20 22,35,38,42,52,55,58,68,73 76 and later e Recurrent laryngeal 9 (3%) 0 (0%) 0 (0%) in combination with a carotidesubclavian (n Z 5)77 81 or nerve injury femoro-axillary bypass (n Z 1).66 Ligation of the SAA was Injury of the brachial 7 (2%) 1 (2%) 0 (0%) fatal in two early reports; both patients died of exsangui- cords nation, on the day of surgery and the 76th postoperative Rebleeding 4 (1%) 0 (0%) 0 (0%) day, respectively.11,42 Aneurysmorraphy was mainly used Unsuccessful ligation 1 (1%) 0 (0%) 0 (0%) for smaller and false aneurysms.19,29,45,50,61,68,75,82,83 Disarticulation 1 (1%) 0 (0%) 0 (0%) Aneurysm resection combined with vein- or polyester- Shoulder instability 8 (3%) 0 (0%) 0 (0%) graft reconstruction provided a useful alternative and was Cardiac complications 4 (1%) 0 (0%) 0 (0%) performed in 51% of cases prior to 1980. Only one proce- Pulmonary 15 (5%) 0 (0%) 0 (0%) dure was reported with fatal outcome, due to a ruptured complications Stanford type-A aortic dissection during surgery in a patient Massive coagulopathy 1 (1%) 0 (0%) 0 (0%) with EhlerseDanlos syndrome.47 In the single-centre series, Cerebrovascular 2 (1%) 0 (0%) 1 (10%) the mortality rate of open repair was 8%, while the overall accident mortality in the surgically treated group was 5%. Seventy- Acute tubular 1 (1%) 0 (0%) 0 (0%) eight percent of treatments were performed in an elec- necrosis tive setting with a mortality rate of 3%, while 18% was carried out in an emergency setting, with a mortality rate of 13%. In the remaining patients, it was unclear whether the procedure was performed in an elective or emergency stent-grafts, but, at the 1-year follow-up, two stent-grafts setting. had occluded. It was concluded that treatment of A variety of postoperative complications have been peripheral aneurysms with stent-grafts not only had a high described following surgical repair (Table 3). Postoperative rate of immediate success, but also had a high incidence of recurrent laryngeal nerve injury was described in 3%.35,43,84 thrombosis.93 Schoder et al. described 10 patients that In 1%, an abscess had to be drained11,42 and seven patients were electively treated with a stent-graft to repair an SAA (2%) developed an ischemic arm, of which four needed due to trauma or a misplaced central venous catheter. The a (partial) amputation.16,50,51 The overall complication rate primary patency at the 1-year follow-up was 100%. Strut was 26%. Systemic complications, such as massive coagul- dislocation without stenosis was observed in one patient opathy, acute tubular necrosis and cerebrovascular acci- and a 50% stenosis, due to compression between the dents, were all reported once.18,36,59 Pulmonary clavicle and the first rib, occurred in another.94 Other complications, including a chylothorax85 and an oesophago- published procedure-related complications include in- pleural fistula38 occurred in 5% of patients and was often stent stenosis,62,96 stent-fracture,96,97 pseudo-aneurysm related to trauma. Paraesthesia due to a brachial cord formation,93,98 early thrombosis95 and wound infection lesion (3%) may be temporary17,19,86 or persistent.29,84,87 In after surgical closure of the groin.98 The overall compli- 2% of cases, the presence or absence of complications was cation rate for EVSAR was 28% with a mortality rate of 5%. not mentioned. Eightypercentofpatientswereoperateduponinan elective setting, with a mortality rate of 4%. The remain- Endovascular and hybrid repair ing 20% were emergency procedures and had a mortality To date, 63 cases of endovascular SAA repair have been rate of 8%. published (Fig. 2a and b). In the mid-1990s, the first Case-series with endovascular treatment have not been endovascular subclavian aneurysm repair (EVSAR) proce- published to date. dures were published. After a follow-up period of 6 months, Fourteen percent of EVSAR procedures were performed no complications were observed.88e92 In 1996, a patient in combination with open techniques,67,99e101 including the died 6 days after an EVSAR, presumably due to pre-existent re-implantation of the SA or vertebral artery in the common cardiac insufficiency.44 Beregi et al. have published a series carotid artery46,102,103 and first-rib resection in case of of 19 patients with peripheral aneurysms, including five TOS.104 SAAs. All SAAs were successfully excluded using various Complications were allocated in the endovascular group. Subclavian Artery Aneurysms 31

embolic complications occurred in proximal SAAs. The risk of thrombo-embolic complications was unrelated to the diameter of the SAA and did also occur in small aneurysms of only 12e25 mm, emphasising that early intervention may be indicated, especially in distal SAAs. As a result of the complication risk, prompt diagnosis and treatment are indicated. In recent years, the number of reported asymptomatic SAAs has increased, due to routine chest X-rays. The non-invasive nature of duplex ultrasound scanning may facilitate early diagnosis. None- theless, nowadays, CTA and MRA are being used more frequently and are likely to become the new gold standard, because of their ability to image the relation of the SAA with its surrounding tissues. Morbidity and mortality rates of open and endovascular repair were within the same range. Mortality rates may be underestimated since the publication of cases may have been partly restricted to successfully treated patients. In the single-centre series, the mortality of open repair was 3% higher, but these included trauma patients that may have increased mortality rates. Complications following EVSAR and hybrid procedures seem to be less severe when compared to those following open repair. Systemic complications were strictly reserved to open surgery as were plexopathy of the brachial cord and injury of the recurrent laryngeal nerve. Endovascular options mainly depend on anatomical characteristics of the aneurysm and access. Especially in trauma25,28,53,61,67,90,93,96,98,105 and iatrogenic SAAs,46,53,60,89,90,94,98,103 EVSAR has proven to be of value. It seems reasonable to assume that emergency repair is associated with an increased mortality. In the present study, 18% of conventional and 20% of endovascular procedures were performed in an emergency setting, with Figure 2 (a) Pre-procedural angiogram of a 36-year old a mortality rate of 13% and 8%, respectively. The great female patient with a middle segment SAA related to TOS. (b) diversity of symptoms and treatment modalities of these Post-procedural angiogram after exclusion of the SAA with patients made a reliable comparison between groups a stentgraft (Viabahn, W.L. Gore & Associates, Flagstaff, AZ, impossible. U.S.A.). The EVSAR was followed by a first rib resection. The SA is extremely mobile and exposed to rotationary forces during abduction and ante-flexion of the arm. Discussion Therefore, a stent-graft, used for EVSAR, has to be flexible and resistant to kinking and fracture. To date, a variety of In the present study, we have shown that a SAA is a rare entity stent-grafts have been used. In-stent stenosis and throm- with <400 published reports in world literature. The true bosis were seen in early series; however, in recent studies, prevalence, however, may well be higher because common patency seems to have increased. Patency results of presentations and adverse outcomes are likely to be under- endovascular treatment may further increase with the reported. This review of the historical literature was based development of better stent-grafts and improved post- entirely on case reports and small series and, therefore, the procedural pharmacotherapy. level of evidence presented is low, as is the nature of In conclusion, we have shown that the SAA is a rare evidence related to other rare conditions. The profile of vascular entity with life- and limb-threatening complica- diagnostic and treatment options of SAAs is changing. While tions. Diagnostic and treatment options are evolving. a mycotic cause is less common nowadays, traumatic and Although guidelines considering the timing of intervention iatrogenic causes are reported more frequently. may not be conducted from available literature, early The occurrence of life- and limb-threatening complica- intervention appears to be indicated, especially in distal tions, such as rupture, embolisation and thrombosis, SAAs, due to the risk of thrombo-embolic complications. seemed to depend on the anatomical localisation of the Endovascular repair and hybrid procedures appear to be the aneurysm. Proximal and mid-clavicular aneurysms had preferred treatment modalities, due to a lower rate of a higher incidence of rupture, when compared to distal cardiopulmonary complications. aneurysms. We could not deduct a diameter at which an SAA should be excluded. Whether other parameters may be better predictors for rupture remain to be elucidated. Conflict of Interest Thrombo-embolic complications were mainly related to distally located aneurysms. Nevertheless, 9% of thrombo- None declared. 32 B.P. Vierhout et al.

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