The Effect of Carotid Calcification on Outcomes of Transfemoral and Transcarotid Artery Stenting in the VQI Michael neilson, MD1 Mahmoud malas, MD, MHS2 Grace wang, MD3 Vikram Kashyap, MD4 Raghu motaganahalli, MBBS4 Marc Schermerhorn, MD5 Jack cronenwett, MD6 Jens Eldrup-Jorgensen, MD1 Brian Nolan, MD1 1-Maine Medical Center, 2-UCSD, 3-UPENN, 4 Indiana University, 5- Beth Israel Deconess, 6-Dartmouth

No disclosures

1 Introduction Carotid artery calcification has been previously reported as a risk factor for post-operative neurologic outcomes following transfemoral carotid stenting (TF-CAS).1 Transcarotid Artery Revascularization (TCAR) has been shown to be safe and effective treatment of carotid stenosis, especially in otherwise high risk individuals.2 1.AbuRahma AF, DerDerian T, Hairi N et al. Anatomic and technical predictors of perioperative clinical outcomes after carotid artery stenting. J Vasc Surg. 2017;66(2): 423-432. 2. Wang Sk, Fajardo A, Sawchuk AP, et al. Outcomes associated with Transcarotid artery revascularization-centered protocol in high risk carotid revascularization using the ENROUE neuroprotection system. J Vasc Surg. 2019;69(3):807-813.

Carotid Calcification in VQI Reported since 2016 Subjective report of degree of calcification of carotid lesion Reported as degree of circumferential calcification <25%, 25-50%, 51-99%, 100% Since 2016 the degree of calcification of the target lesion has been reported to the VQI. This is done in four ranges, ie < 25%, 25-50%, 51-99% or 100% circumferential calcification.

Objective Compare outcomes of TF-CAS and TCAR stratified by degree of circumferential carotid calcification in the VQI

Methods Retrospective cohort study of all CAS in the VQI, 2016-2019 Analyzed by degree of calcification <25%, 25-50%, 51-99%, 100% Primary endpoint Stroke occurring during index hospitalization Secondary Endpoints Major adverse cardiac events (MACE), hemodynamic suppression Multivariate logistic regression analysis to predict carotid calcification MACE included MI, dysrhythmia, or CHF while hemodynamic suppression included hypotension or bradycardia Multivariate logistic regression was used to identify risk factors for carotid calcification

Results Carotid Stenting in VQI, 2016-2019 N=4834 (n=1890) (n=2944) 39% (n=1890) 61% (n=2944) Between 2016 and 2019 there were 4,834 CAS procedures done in the VQI, 61% were TF with 39% being TCAR

Degree of Calicification Patient Demographics Degree of Calicification   <=25% (n=2400) 26-50% (n=885) 51-99% (n=1,361) 100% (n=188) p-value Age 68 71 72 73 0.022 Female 35% 34% 37% 43% 0.050 Symptomatic (stroke or TIA) 61% 64% 60% 0.409 Primary lesion 70% 86% 87% 88% 0.001 Hypertension 84% 91% MI or agina 25% 26% 30% 23% 0.006 Prior PCI or CABG 32% 40% Prior dysrhythmia 16% 20% 24% CHF 14% 19% Current smoker 38% 39% 0.971 COPD 28% 29% 27% ESRD 1% 2% 0.162 Current ASA 83% 85% Current P2Y 73% 78% 80% 71% Current statin Triple therapy 58% 63% 66% Non-white race 13% 10% 9% 0.015 Patient demographics stratified by degree of calcification showed a high burden of traditional risk factors for atherosclerosis, there appeared to be an association between increases degrees of calfication and age, female sex, CHF, and primary lesion as opposed to redo lesion. Increasing degrees of calcification was not associated with symptom status.

Primary Outcomes TCAR p= 0.943 TF-CAS p< 0.001 In terms of our primary outcome, in the tF-CAS cohort there was a statistically significant increasing risk of post-operative neurologic event in those with increasing degree of calcification with a a rate of 2.2% in those with minimal calcification, up to 9.3% in those with 100% calcification. In contrast, those in the TCAR group had no statistically significant deifference in neurologic outcome based on degree of calcification, with a range of 1.2&% to 2.3%. TCAR p= 0.943 TF-CAS p< 0.001

Secondary Outcomes TF-CAS p< 0.001 TCAR p < 0.001 Patients with minimal rates of calcification in the TF-CAS had minimal rates of hemodynamic suppression, while those in the TCAR cohort had increasing rates of hemodynamic suppression with increasing rates of calcification. TF-CAS p< 0.001 TCAR p < 0.001 ** Hypotension and/or bradycardia

Secondary Outcomes TF-CAS p = 0.21 TCAR p = 0.02 Those undergoing TF-CAS had a trend towards increasing MACE for increasing degrees of calcification, though this was not statistically significant. TF-CAS p = 0.21 TCAR p = 0.02

Predictors of Carotid Calcification   OR p value 95% CI Age > 80 2.22 0.001 1.80 2.74 Ae 70 to 79 1.69 1.41 2.03 Age 60 to 69 1.42 1.178 1.714 Atherosclerotic lesion 2.67 2.28 3.10 COPD 1.34 1.17 1.53 CHF 1.27 0.004 1.08 1.51 HTN 1.33 0.002 1.12 1.61 Prior CABG or PCI 1.13 0.048 1.01 1.30 Diabetes 0.015 1.03 Non white race 0.74 0.614 0.90 On multivariate logistric regression, increasing age, as well as a number of co-morbidities including atherosclerotic lesion, COPD< CHF, HTN, prior cardiac intervention and diabetes were also associated with carotic calcification. Non-white race was inversley associated with carotid calcification.

Limitations Self reported degree of calcification within VQI, not adjudicated Retrospective in nature, can only show association, not causation

Summary Increasing degree of calcification is associated with increasing rates of post-operative CVA following TF-CAS This is not seen after TCAR Rate of hemodynamic suppression increases with increasing calcification following both procedures, particularly following TCAR, but this needs further investigation Multiple risk factors for increasing degree of carotid calcification Multiple risk factors for increasing degrees of calcification which may

Conclusions TCAR may be an acceptable alternative even in patients with extensive calcification, though with caution Can predict possibility of carotid calcification which may effect treatment type and pre-operative imaging TCAR may be an acceptable alternative even in patients with extensive calcification, though caution must be taken in regards to possible hemodynamic suppression Further research is needed in the form of a prospective trial to fully elucidate the relationship between carotid calcification and post operative events when considering CAS

Thank You

Degree of Calicification Outcomes Transfemoral Degree of Calicification   <=25% (n=1568) 26-50% (n=512) 51-99% (n=757) 100% (n=107) p-value Postop Neuro event 2.2% 2.9% 4.4% 9.3% 0.001 Postop Hypotension 12% 17% 16% 0.015 Bradycardia 11% 15% 0.034 HD suppression 20% 26% 25% 23% 0.010 Cardiac event 2.8% 2.1% 5.6% 0.21 TCAR <=25% (n=832) 26-50% (n=373) 51-99% (n=604) 100% (n=81) Postop neuro event 2.3% 1.2% 0.943 Postop hypotension 0.004 10% 13% 0.139 21% 39% Postop cardiac event 2.4% 0.3% 2.6% 0.02 In terms of our primary outcome, in the tF-CAS cohort there was a statistically significant increasing risk of post-operative neurologic event in those with increasing degree of calcification with a a rate of 2.2% in those with minimal calcification, up to 9.3% in those with 100% calcification. In contrast, those in the TCAR group had no statistically significant deifference in neurologic outcome based on degree of calcification, with a range of 1.2&% to 2.3%.

Results P=0.001 P=0.001 P=0.04 P=0.253 There was a statistically significant difference between types of interventions at all levels of calcification except at 100% calcification.

Results: Procedural Details Degree of Calicification   <=25% (n=2400) 26-50% (n=885) 51-99% (n=1,361) 100% (n=188) Pre and postdilate 30% 28% 24% 25% Pre dilate only 6% 5% 7% Post dilate 65% 68% 69% 70% The details of the procedure showed that there was an increasing use of post dilation balloon use with increasing degrees of calcification, which was statistically significant. P=.0011