Abstract:

Aim: was to elucidate factors of poor prognosis for chronic brain ischemia in «asymptomatic» patients with atherosclerotic stenosis of vertebral arteries, who regularly take optimal medical therapy.

Methods: in 1st group (n = 44), secondary prevention of cerebrovascular accidents was carried out in a combined strategy - stenting of vertebral arteries in combination with medication therapy, and in 2nd group (n = 56) - only medication therapy. Long-term follow-up was planned after 12, 24 and 36 months. Inclusion criteria: «asymptomatic» patients with stenosis of vertebral arteries 50-95%; diameter of vertebral arteries is not less than 3.0 and not more than 5 mm; presence of cerebral and focal symptoms corresponding to the initial (asymptomatic) stage of chronic brain ischemia (according to E.V. Schmidt). Primary endpoint: total frequency of cardiovascular complications (death, transient ischemic attack or stroke, myocardial infarction).

Results: the total frequency of major cerebral complications over 36 months of follow-up was 4.5% in group 1 and 37.5% in group II (? ²=15.101; p<0.0001). The frequency of cardiac events was 9.1 and 19.6%, respectively, to 1st and 2nd groups (? ²=14.784; p<0.0001). These indicators were obtained against the background of high patient adherence to treatment and high rates of achieving tough target lipid values. Restenosis of stents was observed in general, in 38.67% of patients from group I. Moreover, restenosis alone did not affect the incidence of major cerebral complications in the long-term period (? ²=0.1643; p=0.735). Most significant poor prognosis factors of chronic brain ischemia in «asymptomatic» patients with vertebral artery stenosis, who regularly take optimal medical therapy are: arrhythmia, total cholesterol more than 6.0 mmol/l, incomplete circle of Willis, arterial hypertension, bilateral defeat of vertebral arteries, (low-density lipoprotein) LDL levels of more than 3.5 mmol/I, combined lesion of vertebral and carotid arteries, calcification of vertebral arteries, coronary heart disease in anamnesis.

Conclusion: endovascular intervention in combination with medical therapy could help to avoid the development of major brain complications arising from the instability of atherosclerotic plaque in «asymptomatic» patients with vertebral artery stenosis, and in the presence of poor prognosis factors identified can be regarded as a method of secondary prevention of cerebral circulatory disorders.

References 

1.     Britov AN, Pozdnyakov YuM, Volkova EG, et al. National guidelines on cardiovascular prevention. Kardio-vaskulyarnaya terapiya i profilaktika. 2011;10(6)2: 1-64 [In Russ].

2.     Suslina ZA, Guglevskaja TS, Maksimova MJu, Morgunov VA. Cerebrovascular accidents: diagnosis, treatment, prevention. Moscow: MEDpress-inform, 2016, 440 [In Russ].

3.     Shchukin IA, Lebedeva AV, Burd GS, et al. Chronic cerebral ischemia: syndromological approaches to thera­py. Nevrologiya irevmatologiya. 2015;1:17-24 [In Russ].

4.     Zakharov W, Voznesenskaya TG. Neuropsychiatric Disorders: Diagnostic Tests; podobshch. red. N.N.Yakhno. M.: MEDpress-inform, 2015: 320 [In Russ].

5.     Chechetkin AO, Skrylev SI, Koshheev AJu, et al. Clinical and instrumental assessment of the effectiveness of stenting of the vertebral arteries in the near and remote postoperative periods. Annaly klinicheskoj i jeksperimental'noj nevrologii. 2018;12(3): 13-22 [In Russ].

http://doi.org/10.25692/ACEN.2018.3.2

6.     Sermagambetova ZhN, Maksimova MJu, Skrylev SI, et al. Interventional technologies for the prevention of stroke in the vertebral-basilar system. Consilium Medicum. 2017;19(2): 96-103 [In Russ].

7.     Migunova SG. Clinical and epidemiological study of cerebrovascular diseases and a comparative analysis of the effectiveness of treatment of patients with cerebral atherosclerosis: Diss. kand. med. Ekaterinburg, 2018: 145 [In Russ].

8.     Aboyans V, Ricco JB, Bartelink MEL et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Soci­ety for Vascular Surgery (ESVS). Eur J Vase Endovasc Surg. 2017 Aug 26.

http://doi.org/10.1093/eurhearti/ehx095

9.     Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardio­vascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). European Heart Journal. 2020;41:255-323.

http://doi.org/10.1093/eurhearti/ehz486

10.   Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). European Heart Journal. 2020;41: 111-188.

http://doi.org/10.1093/eurhearti/ehz455

11.   Kamchatnov PR, Umarova HJa, Kabanov AA, Abieva NA. The problem of diagnosis and treatment of patients with vertebrobasilar insufficiency. Lechebnoedelo. 2017;3: 68-75 [In Russ].

12.   Kocak B, Korkmazer B, Islak C, et al. Endovascular treatment of extracranial vertebral artery stenosis. World J. 2012;4:391-400.

http://doi.org/10.4329/wir.v4.i9.391

13.   Markus HS, Larsson SC, Kuker W, et al. VIST Investigators. Stenting for symptomatic vertebral artery stenosis: The Vertebral Artery Ischemia Stenting Trial. Neurology. 2017;89(12):1229-1236.

http://doi.org/10.1212/WNL.00000000000Q4385

14.   Babayan GB, Zorin RA, Pshennikov AS, et al. Predictors of neurological deficiency in hemodynamically significant stenoses of the carotid and vertebral arteries. Nauka molodykh (Eruditio Juvenium). 2019;7(4): 533-540 [In Russ].

http://doi.org/10.23888/HMJ201974533-540

15.   Rakhmonov RA, Todzhiddinov ТВ, Isoeva MB, Zuurbekova DP. Total Cardiovascular Risk - A New Approach to Stroke Prediction. Vestnik Avitsenny. 2017;19(4): 471-475. [In Russ].

http://doi.org/10.25005/2074-0581-2017-19-4-471-475

16.   Shao JX, Ling YA, Du HP, et al. Comparison of hemodynamic changes and prognosis between stenting and standardized medical treatment in patients with symptomatic moderate to severe vertebral artery origin stenosis. M edicine(Baltimore). 2019;98( 13): e14899.

http://doi.org/10.1097/md.0000000000014899

Abstract:

Aim: was to estimate long-term results of vertebral artery (VA) stenting in patients with vertebrobasilar insufficiency (VBI).

Material and methods: study included 194 patients with VBI caused by lesion of V1 segment of VA. All patients received the best course of drug therapy before admission to the clinic. In all these patients, atherosclerotic stenosis of 70% or more of VA was revealed in V1 sergment. All patients underwent surgical correction of V1 segment of VA. Open surgery was performed in «A» group – with a tortuosity of VA – 129(66,5%), in group «B» – without tortuosity of a VA – 65(33,5%) performed stenting of V1 segment of PA.

Bare-metal stents were implanted in 44 patients, drug-eluted stents - 14, renal stents – 7. Distal protection was used in 14 patients. In remaining patients, stenting was performed without embolic protection devices.

Main criteria for evaluating of results were: patency of the reconstruction zone and clinical improvement in the patient after surgery. Statistical processing of results was carried out by calculating ?2, the exact Fisher test (EFT) and constructing of Kaplan-Meier survival curves.

Results: it was determined that in «hopeless» patients, from the point of view of drug treatment, it is possible to achieve a significant clinical effect by surgical methods. Of 194 patients, clinical improvement in the early postoperative period was achieved in 189(97,4%) patients, after 1 year in 177 (91,2%) patients, and after 3 years in 156(80.2%) patients.

In case of stenting of V1 segment of VA – we received excellent immediate results – 100% of technical and clinical success. However, in the long term, results of open operations were better than results of stenting. 3 years after operation, a higher clinical efficacy of open methods was determined – 79,8%, in contrast to stenting – 73,8%. Although, differences were not statistically significant (p> 0,05). 3 years after operation, in case of open operations, a significantly smaller number of restenosis of the reconstruction zone was 1.6%, than with stenting – 15,4% (p <0.05). However, in patients with open operations, more thrombosis of the reconstruction zone were revealed – 5,5% than in patients with stenting – 1.5% (p>0,05). When performing open operations on V1 segment of VA, strokes were fewer – 2.3%, than in group of V1 stenting segment of VA – 3.1% (p> 0.05). When comparing Kaplan-Meyer curves, the median during open surgeries on VA is not achieved after 18 years, and in group of stenting of VA, it occurs after 7 years.

Conclusion: stenting of V1 segment of vertebral arteries in patients with VBI is not the operation of choice in terms of long-term results. However, this operation can be considered as the first stage of brain revascularization in the presence of significant stenosis of V1 segment of vertebral artery and low brain tolerance to ischemia in patients with multiple lesions of brachiocephalic arteries.

References

1.     Savitz SI, Caplan LR: Vertebrobasilar disease. N Engl J Med. 2005; 352:2618-2626.

2.     Caplan LR, Wityk RJ, Glass TA, Tapia J, Pazdera L, Chang HM, Teal P, Dashe JF, Chaves CJ, Breen JC, Vemmos K, Amarenco P, Tettenborn B, Leary M, Estol C, Dewitt LD, Pessin MS: New England Medical Center Posterior Circulation registry. Ann Neurol. 2004; 56:389-398.

3.     Vereschagin NV. Pathology of vertebrobasilar system and cerebrovascular accidents. M. 1980; 312. [In Russ].

4.     Puzin MN, Zinoveva GA, МеtelkinaLP. Aspects of medical treatment of patients with vertebrobasilar insufficiency. Klinicheskaya farmakologiya i terapia, 2006; 2: 23-26. [In Russ].

5.     Berguer R, Morasch M, Kline R. A review of 100 consecutive reconstructions of the distal vertebral artery for embolic and hemodynamic disease. J Vasc Surg. 1998; 27 (5): 852-859.

6.     Pokrovskii AV, Belojarcev DF. Long-term results of operations subclavian-carotid transposition. Angiologiya i sosudistaya khirurgiya 2002; 8 (2): 84 - 91. [In Russ].

7.     He Y, Bai W, Li T et al. Perioperative complications of recanalization and stenting for symptomatic nonacute vertebrobasilar arteryocclusion. Ann Vasc Surg. 2014 Feb; 28 (2):386-393.

8.     2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018 Mar 1; 39(9): 763-816.

9.     National guidelines on the management of patients with brachiocephalic artery disease. Angiologiya i sosudistaya khirurgiya. 2013; 19 (2), appendix: 70 [In Russ].

10.   Schonewille WJ, Algra A, Serena J, Molina CA, Kappelle LJ. Outcome in patients with basilar artery occlusiontreated conventionally. J Neurol Neurosurg Psychiatry. 2005; 76:1238-1241.

11.   Coward LJ, McCabe DJ, Ederle J, Featherstone RL, Clifton A, Brown MM: Long-term outcome after angioplasty and stenting for symptomatic vertebral artery stenosis compared with medical treatment in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomized trial. Stroke. 2007; 38:1526-1530.

12.   Compter A, van der Worp HB, Schonewille WJ, Vos JA, Algra A, Lo TH, Mali WPThM, Moll FL and Kappelle LJ. VAST: Vertebral Artery Stenting Trial. Protocol for a randomized safety and feasibility trial. Trials 2008; 9: 65.

13.   Clifton A, Markus H, Kuker W, Rothwell P.E-050. The Rationale for the Vertebral artery Ischaemia Stenting trial (VIST): NeuroIntervent Surg 2013; 5. Suppl 2 A56.

14.   Compter A et al. VAST investigators. Stenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial. Lancet Neurol. 2015 Jun; 14(6): 606-614.

15.   VIST (Vertebral artery Ischaemia Stenting Trial) ISRCT N 95212240.

16.   Markus HS, Harshfield EL, Compter A. et al. Stenting for symptomatic vertebral artery stenosis: a preplanned pooled individual patient data analysis. Lancet Neurol. 2019 Jul; 18(7): 666-673.

https://doi.org/10.1016/S1474-4422(19)30149-8

17.   Markus HS, Larsson SC, Dennis J et al. Vertebral artery stenting to prevent recurrent stroke in symptomatic vertebral artery stenosis: the VIST RCT. Health Technol Assess. 2019 Aug; 23(41): 1-30.

Abstract:

Aim: was to estimate the importance of restoring blood flow in vertebral arteries in the segment V1 by stenting in patients with multivessel lesions of extracranial arteries and vertebrobasilar insufficiency (VBI).

Material and methods: study include 59 patients with a dominant, long-existing clinic of vertebrobasilar insufficiency, with multivessel lesions of brachiocephalic arteries, lower brain tolerance to ischemia, with the presence of stenosis of segment V1 of vertebral artery more than 70%, which is regarded by neurologists, as the main reason for VBI. All patients should have been undergone carotid revascularization. However, due to multivessel lesions and low perfusion reserve, all patients as the first stage of treatment - underwent stenting of V1 segment of vertebral artery. In 38 patients bare-metal stent were used, in 14 - drug-eluting stents, in 7 - renal stents. Distal protection was used in 12 patients. In remaining patients - stenting was performed without protection.

Results: in immediate postoperative period, technical, angiographic success and clinical improvement were noticed in 100% of patients. All 59 patients underwent the second and subsequent stages of cerebral revascularization without ischemic episodes. The duration of follow-up was from 6 months to 6 years. After 3 months, 55(93,2%) patients sustained clinical improvement, with no restenosis in stents. 4 patients (6,8%) had no clinical improvement: in one patient after 3 months developed ischemic stroke (IS) in vertebrobasilar system(VBS), due to the occlusion of the stent. 1 patients had stent restenosis with the increase of clinical manifestations of VBI, which required additional stenting. After 14 months, 1 patient after stenting had IS in VBS due to stent fractures caused by bone compression.

Conclusion: stenting of V1 segment of vertebral artery in patients with multivessel lesions of brachiocephalic arteries and clinic of VBI, can be considered as the first stage of cerebral revascularization in case of significant stenosis segment V1 vertebral artery and low tolerance to cerebral ischemia.

References

1.     Savitz S.I., Caplan L.R. Vertebrobasilar disease. N Engl J Med. 2005, 352: 2618-2626.

2.     Caplan L.R., Wityk R.J., Glass T.A., Tapia J., Pazdera L., Chang H.M., Teal P, Dashe J.F., Chaves C.J., Breen J.C., Vemmos K., Amarenco P, Tettenborn B., Leary M., Estol C., Dewitt L.D., Pessin M.S. New England Medical

Center Posterior Circulation registry. Ann Neurol. 2004, 56: 389-398.

3.     Vereshhagin N.V. Patologija vertebral'no-baziljarnoj sistemy i narushenija mozgovogo krovoobrashhenija[Pathology of vertebrobasilar system and cerebral blood flow disorders]. M. 1980; S 28 [In Russ].

4.     Puzin M.N., Zinov'eva G.A., Metelkina L.P. Aspekty medikamentoznogo lechenija bol'nyh s vertebral'no-baziljarnoj nedostatochnost'ju [Aspects of pharmacotherapy in treatment of patients with vertebrobasilar insufficiency]. Klinicheskaja farmakologija i terapija. 2006; 2: 23-26 [In Russ].

5.     Berguer R., Morasch M., Kline R. A review of 100 consecutive reconstructions of the distal vertebraf artery for embolic and hemodynamic disease. J Vasc Surg. 1998, 27 (5): 852-859.

6.     Pokrovskiy A.V., Beloyartsev D.F., Otdalemmie rezultati operatsiy podkluchichno-sonnoi transpozitsii. [Longterm results of operations of the subclavian-carotid transposition.] Angiologia I sosudistaya khirurgia. 2002; 8(2): 84-91.

7.     He Y, Bai W., Li T. et al. Perioperative complications of recanalization and stenting for symptomatic nonacute vertebrobasilar arteryocclusion. Ann Vasc Surg. 2014 Feb; 28 (2): 386-393.

8.     European Stroke Organisation et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2011 Nov; 32 (22): 2851-906.

9.     Natsionalnie rekomendacii po vedeniyu patsientov s zabolevaniyami brakhiotsefal’nikh arteriy. [National guidelines on the management of patients with diseases of brachiocephalic arteries.] Angiologia I sosudistaya khirurgia. 2013; 19 (2): attachment 70.

10.   Schonewille W.J., Algra A., Serena J., Molina C.A., Kappelle L.J. Outcome in patients with basilar artery occlusion treated conventionally. J Neurol Neurosurg Psychiatry. 2005, 76:1238-1241.

11.   Coward L.J., McCabe D.J., Ederle J., Featherstone R.L., Clifton A., Brown M.M. Long-term outcome after angioplasty and stenting for symptomatic vertebral artery stenosis compared with medical treatment in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomized trial. Stroke. 2007, 38: 1526-1530.

12.   Compter A., van der Worp H.B., Schonewille W.J., Vos J.A., Algra .A., Lo T.H., Mali WPThM, Moll FL. and Kappelle L.J. VAST: Vertebral Artery Stenting Trial. Protocol for a randomised safety and feasibility trial. Trials 2008, 9: 65.

13.   Clifton A., Markus H., Kuker W., Rothwell P. E-050. The Rationale for the Vertebral artery Ischaemia Stenting trial (VIST): NeuroIntervent Surg 2013; 5. Suppl 2 A56.

14.   Compter A., et al. VAST investigators. Stenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial. Lancet Neurol. 2015 Jun; 14(6): 606-614.

15.   VIST (Vertebral artery Ischaemia Stenting Trial) ISRCT N 95212240.