Variations in branching pattern of the arch of aorta have been well studied. Numerous variations have been observed and well documented. The wide spectrum of variations in the anatomical arrangement of the human aortic arch and its branches offers valuable information for safely performing endovascular surgery by aiding in the catheterization of the aortic arch and its branches. Furthermore, there is a slight difference in the cerebral haemodynamics of individuals with such variations. This paper aims to substantiate the existence of these variations, highlight their clinical implications, and establish a correlation with embryological development. The brain develops from neuroectoderm during the third week of gestation and blood vessels develop from the mesoderm in the order of anterior circulation system and posterior circulation system. The aortic arch forms as a pair in the ventral and dorsal areas, and six arches develop between the aorta during the initial period of gestation, undergoing a degeneration process. During the 4 mm embryonic period, the 1st and 2nd aortic arch degenerate as the 3rd and the 4th aortic arch appears. In the 12 mm embryonic period, the dorsal blood vessel in the 3rd aortic arch degenerates. The remaining segment of the 3rd aortic arch in the dorsal area forms the left carotid artery as well as the left subclavian artery (LSA) in the cervical vertebral segment. By the 40 mm embryonic period, the residual part of the dorsal blood vessels of 3rd aortic arch forms brachiocephalic trunk (BCT), while the 4th aortic arch forms the normal adult-type aortic arch, including BCT, left common carotid artery (LCCA), and LSA.1,2 Changes involved in the Aortic Arch system such as regression, retention, or reappearance result in the variations in branching pattern of aortic arch. Variations on this branching pattern are likely to occur as a result of the altered development of certain branchial arch arteries during the embryonic period of gestation.3 Variations in the origin of the great vessels of the aortic arch and the pulmonary trunk may result from irregular and imperfect development of the aortico-pulmonary septum of the truncus arteriosus. Normally the first part of vertebral artery develops from the dorsal ramus of the seventh intersegmental artery. The left subclavian artery develops solely from the left seventh intersegmental artery. In cases where the vertebral artery arises as a branch from the arch of the aorta, it is explained embryologically that this occurs because the vertebral artery develops from a persistent sixth cervical intersegmental artery. When segments of the dorsal aorta fail to disappear, blood flows through these persistent routes. The left limb of the aortic sac normally forms the part of the arch that intervenes between the origins of the brachiocephalic trunk and the left common carotid artery. If the aortic sac fails to bifurcate into right and left limbs, the left common carotid artery will connect directly to the aortic sac, resulting in a common origin of the carotid arteries. The abnormal brachiocephalic trunk (consisting of only two trunks from the arch – RBCT & LBCT) forms due to the fusion of the proximal part of the left third arch artery and the left seventh intersegmental artery into the left fourth artery, which may later be responsible for the formation of the carotid and subclavian arteries from the common trunk. The branching pattern of the brachiocephalic trunk varies because the proximal part of the third aortic arch normally extends and is absorbed into the left horn of the aortic sac. If it is absorbed into the right horn of the aortic sac, these variations occur.4

The collection of samples is done from the Anatomy department of Shri Atal Bihari Vajpayee Medical College and Research Institute, Bangalore. Hearts along with the Arch of aorta from the formalin fixed cadavers are taken as samples. A total of 50 hearts are observed for variations in the branching pattern of the aortic arch. Careful dissection is performed on the 10% formalin-fixed cadavers in which the excess fasciae were removed leaving the necessary nerves, great vessels, tissues and organs in situ. The tissues surrounding the aortic arch and its branches were stripped off to fully expose them. The original position was observed and photographed. A description of the aortic arch and its branching pattern was recorded. Inclusion criteria: Cadavers of all ages and both genders received for the dissection classes. Exclusion criteria: Cadavers with cutting or crushing injury to the Arch of Aorta.

Of the 50 hearts examined, the most common type is type 1 where the BCT, LCCA and LSA arise separately from AA with 46(92%) specimens. Variations were observed in 4 (8%) specimens. 2(4%) of them were type 2 Common Trunk type(Bovine type) where the BCT and the LCCA had a single common trunk arising from the AA. The other 2(4%) was of type 3 Left Vertebral artery type, where the LVA arises directly from the AA between the origin of LCCA and LSA. TABLE 1: Present Study. TYPE PRESENT STUDY 1(Normal) 92% 2(Bovine) 4% 3(Left Vertebral) 4% 4(Bovine &Left Vertebral) ----- 5(Common Carotid) ----- 6(Aberrant Rt. Subclavian) ----- 7(Rt. Arch) -----

TABLE 2 : Description of types of Aortic Arch variations. Type Description Type 1 Most common type. BCT, LCCA & LSA arise separately from AA Type 2 BCT & LCCA arise from a common trunk branching from AA Type 3 LVA arises independently from AA between LCCA & LSA Type 4 Combination of type 2 & type 3. BCT & LCCA arise as common trunk from AA. LVA arises separately from AA before LSA Type 5 RCCA & LCCA have a common trunk whereas RSA & LSA arise separately from AA Type 6 RSA arises from descending aorta Type 7 Aortic arch is to the right i.e., exact opposite of type 1 No statistically significant differences were found in comparing cadaveric with imaging studies.7 With increasing rates of neck and chest surgery, it is exceedingly crucial to have a thorough understanding of the anatomic variation of the AA.8,9 Of the 7 types described above, 3 types i.e., type 1,2 & 3 were encountered in the present study. Of these, type 1 is considered normal and the rest as variations. According to Bernardi and Dettori (1975), the abnormal origin of vertebral artery may favor cerebral vascular disorders because of alterations in cerebral heamodynamics.5 According to Yong-Gu Chung et al, in 8% cadavers, BCT and LCCA originated together while LSA originated independently from AA. In another 8%, the regular branches and LVA branch independently from AA.6 As per meta-analysis by Patrick Popieluszko et al, of a total of 51 studies, the most common pattern was type 1, an AA that goes from right to left, giving off a BCT, an LCC, and an LS, with an overall incidence of 80.9%. The second most common was type 2, the bovine arch, with an incidence of 13.6%, followed by type 3, arches with the LVA coming off the AA, with 2.9%. The pooled other category accounted for 1%. The normal AA, designated type 1, was decisively the most common variant, followed by type 2 (bovine arch), then type 3 (LV). The other four remaining most common variants were identified as the type 4 (bovine and LV), type 5 (common carotid),type 6 (aberrant RSA), and type 7 (right arch), each of which had an incidence of <1%. All patterns outside of these seven accounted for about 1%.7 The present study is consistent with the above meta-analysis with type 1 being the most common followed by type 2 bovine & type 3 LVA in equal numbers. In a study by Williams GD, Edmonds HW, South American and African populations demonstrated significantly higher incidences of type 2 (bovine arch) variants, with 24.2% and 26.8%, respectively. These results could reflect genetic factors at play in these populations. The earliest included study from North America report that subjects of African descent showed a prevalence of bovine arch twice as high as that of whites, further supporting that race can play a major factor in AA anomalies.10 In a study by Qiu Y, Wu X, Zhuang Z, Li X, Zhu L, Huang C et al, 106 of the 120 cadavers had normal aortic arch branches and gave rise to usual branches, namely the BCT, the LCCA and the LSA. The remaining 14 cadavers had 2 basic types of branch variations, thus accounting for an incidence of 11.67%. A total of 9 aortic arches emitted 4 branches; the brachiocephalic trunk, the left common carotid artery, the left vertebral artery and the left subclavian artery (incidence 7.5%). The second subgroup of 5 cadavers also emitted 4 aortic branches: the right common carotid artery, the left common carotid artery, the left subclavian artery and the right subclavian artery (incidence 4.16%). In this group, the right subclavian artery sprung as a distal branch of the aortic arch (descending), thus making a vascular ring that takes a supero-posterior course round the back of the trachea and the oesophagus to reach the right side. There was a single cadaver, different from the other 4 aortic branches of the second group which had a common origin for the common carotid arteries, while the left subclavian artery and distally placed right subclavian artery were present.11 Virendra Budhiraja, Rakhi Rastogi et al demonstrated in thirty-three (63.5%) cadavers, the aortic arch showed classical branching pattern which includes brachiocephalic trunk, left common carotid artery, and left subclavian artery. In nineteen(36.5%) cadavers it showed variations in the branching pattern, which include the two branches, namely, left subclavian artery and a common trunk in 19.2% cases, four branches, namely, brachiocephalic trunk, left common carotid artery, left vertebral artery, and left subclavian artery in 15.3% cases, and the three branches, namely, common trunk, left vertebral artery, and left subclavian artery in 1.9% cases.12 According to Pasaoglu Lale, Ugur Toprak et al, of 881 patients, 770 (87.4%) patients with classic branching pattern of the aortic arch (AA) were observed. Variations in branching pattern were seen in 111 (12.6%) patients. The most common variation was the origination of the left common carotid artery (LCCA) from the brachiocephalic trunk (BCT). This pattern was observed in 64 (7.2%) cases. In 25(2.8%) cases, the left vertebral artery (LVA) originated directly from the AA between the origin of the LCCA and LSA. 17 (1.9%) cases had aberrant right subclavian artery. Three (0.3%) cases showed right aortic arch. Two cases had right aortic arch with aberrant left subclavian artery.13 Yamaki et al examined the branch of the vertebral artery in 515 Japanese adult cadavers. In one cadaver, the right vertebral artery originated from the BCT. In 30 cadavers (5.8%), it directly originated from the aortic arch between the left vertebral artery and the left common carotid artery.14 Matula et al reported that among 190 cases, there were four cases (2.5%) in which the left vertebral artery originated directly from the aortic arch.15 Such results were comparable to our results. As per the CT angiographic study by G.Vucurevic, S.Marinkovic et al, of the 1266 patients, 946 (74.72%) had usual type 1 branching of AA. Of the remaining 320 (25.28%) variations, bovine type branching of AA was seen in 197 (15.56%) patients, LVA from AA was seen in 46 (3.63%) patients and the rest 77 (6.09%) showed various other branching such as 2 vessel, 5 vessel patterns etc.16 According to thoracic Angio-computed tomography scans’ study of 92 living patients by Stefanos Demertzis, Samuel Hurni et al Normal anatomy was encountered in 82(89.13%) patients. Among the remaining 10 patients, there were 8(8.7%) with a common origin of the right and left common carotid artery and in 2(2.17%) instances there were separate origins of the right subclavian artery directly from the aortic arch.17 Study by Rekha P et al showed, the usual three branched aortic arch was found in about 92.72% and five types of variations were found in the remaining. 4.5% had the left vertebral artery arising as branch of aortic arch between origins of left common carotid artery and left subclavian artery, 2.72% showed a common origin of brachiocephalic trunk and left common carotid artery, 0.90% presented with two branches arising from arch of aorta, 0.90% showed that brachiocephalic trunk giving rise to left common carotid artery.18 According to a study by Pandalai U, Pillay M, Moorthy S et al, the variations included seven cases (25.9%) of aberrant right subclavian artery, one case of bovine arch, one case of bovine origin of left vertebral artery from arch, one case of bronchial artery of anomalous origin from arch, one case of double aortic arch, and 16 cases of right-sided aortic arch.19 K Mohan, Kumar D demonstrated that the usual three-branched pattern of arch of aorta was found in 44 specimens (78.33%). The common trunk for both brachiocephalic trunk and left common carotid artery was present in 11 specimens (18.33%). In 2 specimens (3.33%), the arch gives four branches.20 As per a study by Radhakrishna Shetty K, Bhat Shivarama P et al, normal anatomical branching pattern with three branches were observed in 38 aortic arches (76%) and a pattern showing 2 branches were noted in 8 aortic arches(16%) and 4(8%) aortic arches showed four branches.21 Clinical significance of these variations in aortic arches have been documented in various previous studies. A study conducted by Tapia et al in 2015 suggested that different anatomic variations of the AA may provide insight into the initial tearing site in aortic dissection. Most notably, they concluded that patients with a left vertebral (LV) pattern were more likely to develop a Stanford type B dissection.22 As per Celikyay ZR et al Type 2 (bovine arch) pattern has been documented as making carotid stenting more difficult and riskier, depending on the approach. This difficulty may be encountered as a result of a tight turn involving the BT and the LCC arteries on stenting through a femoral approach.23 Dumfarth J et al state, therefore, patients identified as having a bovine arch may benefit from a brachial approach, a radial one, or a novel trans-carotid artery revascularization procedure. In addition, it has been shown that patients with a bovine arch pattern are more likely to need hemiarch replacement surgery in treating AA disease, including aortic dilation, dissection, intramural hematoma, and rupture of the aorta. In addition to surgical risk factors, the bovine arch pattern may be a biomarker for the aforementioned aortic diseases.24 Preparing for such complications or simply choosing a less risky approach like a branchial or radial approach as a standard may diminish this risk in the significant portion of the population that has the bovine arch variant. TABLE 3 : Comparison of various cadaveric studies TYPE Present study Patrick Popieluszkol7 Young6 QiuY11 Rakhi12 Rekha P18 Mohan K20 Bhat21 1(Normal) 92% 80.9% 84% 88.3% 63.5% 92.7% 78.33% 76% 2(Bovine) 4% 13.6% 8% ----- 19.2% 2.72% 18.33% 16% 3(Left Vertebral) 4% 2.9% 8% 7.5% 15.% 4.5% 3.33% 08% 4(Bovine & Left Vertebral) ----- 1% ----- ----- 1.9% ----- ----- ----- 5(Common Carotid) ----- 1% ----- <1% ----- ----- ----- ----- 6(Aberrant Rt. Subclavian) ----- <1% ----- 4.16% ----- ----- ----- ----- 7(Rt. Arch) ----- <1% ----- ----- ----- ----- ----- ----- TABLE 4: Comparison with radiological studies TYPE Present study Patrick Popieluszkol et al 7 Pasaoglu Lale et al 13 Matula C et al 15 G.Vucurevic et al 16 Stefanos D et al 17 1(Normal) 92% 80.9% 87.4% 97.5% 74.72% 89.13% 2(Bovine) 4% 13.6% 7.2% ----- 15.56% ----- 3(Left Vertebral) 4% 2.9% 2.8% 2.5% 3.36% ----- 4(Bovine & Left Vertebral) ----- 1% ----- ----- 6.09% ----- 5(Common Carotid) ----- 1% ----- ----- ----- 8.7% 6(Aberrant Rt. Subclavian) ----- <1% 1.9% ----- ----- 2.17% 7(Rt. Arch) ----- <1% 0.3% ----- ----- -----

The results show that the prevalence of such variations is not rare. The clinical relevance of this in catheterization, endovascular surgery and artery dissection needs to be well understood. This will prevent unforeseen catastrophes, as such branching patterns may cause complications during procedures. The understanding and acknowledgement of its prevalence and importance is all the more essential as shown by the results of this paper. Abbreviations: AA: Arch of Aorta RCCA: Right common carotid artery. LCCA: Left common carotid artery BCT: Brachiocephalic trunk LVA: Left vertebral artery RSA: Right subclavian artery LSA: Left subclavian artery.

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