B. PATRICE MWIPATAYI, MMed, FCS (SA), FRACS, GD-CLINED (Melb)

Department of Vascular Surgery, RPH

School of Surgery, University of Western Australia Perth.

Director of Perth Institute of Vascular Research (PIVAR)

PREDICTORS OF PERI-PROCEDURAL OUTCOMES OF CAS

A REAL WORLD EXPERIENCE

Rhys Daniel, MBBS, Chem.Eng

Jackie Wong, MPH

DISCLOSURE

Speaker name: Prof. B. Patrice Mwipatayi

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

• RCTs have shown Carotid Intervention by CEA or CAS are efficacious

• Trend of improving CAS results with experience and newer devices

• 30-day STROKE or DEATH RATE

RCT (ICSS, EVA 3S, CREST, SPACE): 6.7- 9.6%

Registries: 0-12%

INTRODUCTION - PPPH-CAS

Kolkert JL, Meerwaldt R, Geelkerken RH, Zeebregts CJ. Endarterectomy or carotid artery stenting: The quest continues part two. Am J Surg, 2015 Feb ; 209(2):403-12

INTRODUCTION - PPPH-CAS

• Hemodynamic alterations such as bradycardia or hypotension are well-

recognized physiological responses during CAS, but most of these events are

transient and self-limiting in nature. 1, 2

• The incidence of hypotension during CAS ranges widely, from 14% to 28%, based

on available reports.1

• Nearly 60% of all hypotension patients developed during the procedure and 41%

after the procedure.

1. Mlekusch W, Schillinger M, Sabeti S, et al. Hypotension and bradycardia after elective carotid stenting: frequency

and risk factors. J Endovasc Ther. 2003 Oct;10(5):851-859..

2. McKevitt FM, Sivaguru A, Venables GS, et al. Effect of treatment of carotid artery stenosis on blood pressure: a comparison of

hemodynamic disturbances after carotid endarterectomy and endovascular treatment. Stroke. 2003 Nov;34(11):2576-2581

INTRODUCTION - PPPH-CAS

• Prolonged Post-Procedural Hypotension (PPPH-CAS) was defined as a FALL IN

SYSTOLIC BLOOD PRESSURE (SBP) OF >30MMHG FROM BASELINE WITHOUT EVIDENCE OF

HYPOVOLEMIA, WITH A SYSTOLIC PRESSURE (SBP) < 90 MM HG AT THE END OF CAS AND

LASTING AT LEAST 1-2 HOURS. 1, 2

• The concern about the POTENTIAL HARMFULNESS OF HYPOTENSION AND BRADYCARDIA

during or after CAS has enhanced the scientific interest about its risk factors.

• SO FAR, THE REPORTED PREDICTORS VARY FROM ONE STUDY TO ANOTHER.

•1. George Dangas,, John R. Laird, Jr, Lowell F. Satler et al. Postprocedural Hypotension after Carotid Artery Stent Placement: Predictors and Short- and Long-term

Clinical Outcomes. Radiology, Jun 2000, Vol. 215:677–683.

•2. T. NONAKA, S. OKA, S. MIYATA, T. BABA, T. MIKAMI, K. HOUKIN. Risk Factors of Postprocedural Hypotension Following Carotid Artery Stenting. 2006 Jan; 12(Suppl

1): 205–210.

DEFINITION OF PPPH-CAS

INTRODUCTION - PPPH-CAS

Atropine Sulfate (0.5 mg) ivi

Persistence of Bradycardia and Hypotension

Repeat Atropine (up to 0.04/kg)

Or

Repeat Glycopyrrolate (300 ug) ivi

Aramine: 0.5-5mg, follow by an adjusted infusion rate

(15-100mg/500ml N/S)

SBP > 90mmHg

Continue with IVI crystalloid fluid

Admit to HDU for monitoring

and continuous management

Or Glycopyrrolate (300 ug) iviOR

PIVAR

PPPH-CAS

To describe the predictors of persistent hypotension after CAS

placement.

To define the clinical outcome of patients with this

hemodynamic disturbance (stroke and death rate at 30 days)

STUDY AIM

PRECISE PRO RX® CAROTID STENT SYSTEM1. Micromesh geometry− ‘V’ pattern mesh structure − Peak-to-valley design − Optimal free-cell area 2. SAPPHIRE Trial(n=334)− Non-inferiority of PCAS vs CEA in high-risk patients − PCAS durability at 3 years follow-up

XACT® CAROTID STENT SYSTEM1. close cell design and a high radial force generated by the variable size of the cells.2. SECuRITY trial was a prospective, multi-center registry that reported on 305 high-risk patients at 30 sites

CRISTALLO IDEALE CAROTID STENTThe hybrid stent design is able to combine both the flexibility of an open-cell structure and the resistance to particle penetration of closed-cell structures.

STENT CHOICE : PPPH-CAS

CHARACTERISTICS No PPPH-CAS(n=123)

PPH-CAS(n=37)

Total(n=160)

Age (mean ± SD) 73.28 ± 9.08 70.46 ±11.66

72.63 ± 9.77

Age ≥ 65yr – no. (%) 105 (85.4) 26 (70.3) 131 (81.9)

Male sex - no. (%) 89 (72.3) 27 (73.0) 116 (72.5)

White race - no. (%) 117 (95.1) 36 (97.3) 153 (92.2)

CHARACTERISTICS No PPPH-CAS(n=123)

PPH-CAS(n=37)

Total(n=160)

Smoking – no. (%) 32 (26.0) 15 (40.5) 47 (29.4)

Diabetes Mellitus – no. (%) 37 (30.0) 16 (43.2) 53 (33.1)

Arrythmia – no. (%) 22 (17.9) 7 (18.9) 29 (18.1)

CAD – no. (%) 56 (45.5) 13 (35.1) 69 (43.1)

CABG – no. (%) 14 (11.4) 1 (2.7) 15 (9.4)

Hypertension – no. (%) 102 (82.9) 29 (78.4) 131 (81.9)

Hyperlipidemia – no. (%) 69 (56.1) 26 (70.3) 95 (59.4)

Previous CVA – no. (%) 16 (13.0) 4 (10.8) 20 (12.5)

CRF – no. (%) 20 (16.2) 1 (2.7) 21 (13.1)

PVD – no. (%) 57 (46.3) 16 (43.2) 73 (45.6)

Previous malignancy – no. (%) 9 (7.3) 4 (10.8) 13 (8.1)

Smoking – no. (%) 32 (26.0) 15 (40.5) 47 (29.4)

PATIENT DEMOGRAPHIC

INDICATION FOR INTERVENTION

CHARACTERISTICS No PPPH-CAS(n=123)

PPH-CAS(n=37)

Total(n=160)

TIA – no. (%) 33 (26.8) 10 (27.0) 43 (26.9)

Amaurosis Fugax 28 (22.8) 5 (13.5) 33 (20.6)

CAS/CEA 12 (9.7) 4 (10.8) 16 (10.0)

Pre-CABG CAS 5 (4.0) 1 (2.7) 6 (3.8)

Restenosis after surgery 9 (7.3) 0 (0) 9 (5.6)

Symptomatic – no. (%) 71 (57.7) 20 (54.0) 91 (56.9)

LESION CHARACTERISTICS AT BASELINE

CHARACTERISTICNo PPPH-CAS

(n = 123)PPH-CAS(n= 37)

P Value

LESION SIDE (%)Right side 67 (54.5) 17 (45.9) ….

ARCH TYPE (%)

Type I 53 (43.1) 15 (40.5) 0.851

Type II 59 (48.0) 19 (51.3) 0.718

Type III 2 (1.6) 2 (5.4) 0.197

Bovine Arch 9 (7.3) 1 (2.7) 0.309

LESION CALCIFICATION (%)

None - Mild 40 (32.6) 5 (13.5) ….

Moderate 69 (56.1) 21 (56.8) ….

Severe 14 (11.4) 11 (29.7) ….

DEGREE OF CONTRALATERAL CAROTID ARTERY STENOSIS (%)

Normal – mild disease 75 (61) 23 (62.2) ….

70 – 99% 45 (36.6) 14 (37.8) ….

Occluded 3 (2.4) 0 (0) ….

LESION LENGTH (MM) MEAN± SD 24.21 ± 4.06 24.24 ± 4.58 0.611

CLINICAL CHARACTERISTICS AT BASELINE

CHARACTERISTICNo PPPH-CAS

(n = 123)PPH-CAS(n= 37)

P-value

SBP pre-procedure (mmHg) 145.9 ± 10.7 141.6 ± 13.2 0.077

SBP after stent implantation (mmHg) 138.2 ± 14.5 85.5 ± 4.0 < 0.001

Hb, g/L (pre-procedure) 130.1 ± 15.9 132.6 ± 21.4 0.139

Hb, g/L (post-procedure) 119.5 ± 16.1 123.1 ± 20.5 0.211

ASA physical status

ASA 2 26 (21.1) 6 (16.2)

ASA 3 85 (69.1) 28 (75.7)

ASA 4 12 (80) 3 (8.1)

Number anti-Hypertensive Medications – mean (SD/range) 2.41 ± 1.29 2.11 ± 1.39 0.120

Modified Rankin Scale

0 - 2 122 (99.2) 37 (100)

3 - 5 1 (0.8) 0

LOS-ICU (days) 1.16 ± 0.43 2.32 ± 0.88 < 0.001

LOS-Hospital (days) 2.88 ± 1.84 4.16 ± 1.86 < 0.001

DEVICE AND PROCEDURAL CHARACTERISTICS AT BASELINE

CHARACTERISTICNo PPPH-CAS

(n = 123)PPH-CAS(n= 37)

P-value

PRIMARY STENTING 38 (30.9) 17 (45.9) 0.091

EMBOLIC PROTECTION DEVICE

FilterWire EZ™ 51 (41.5) 13 (35.1) …

Emboshield NAV6 35 (28.5) 5 (9.3) …

Angioguard™ 31 (25.2) 19 (51.4) …

Other EPD* 2 (1.6) 0 (0) …

STENT TYPE

Precise Pro Rx® Carotid Stent 44 (35.8) 27 (73) < 0.001

Xact® Carotid Stent 50 (40.6) 5 (13.5) 0.004

Cristallo Ideale ® 20 (16.3) 4 (10.8) 0.4190

Other stents** 9 (7.3) 1 (2.7) 0.3295

STENT DIAMETER 8.36 ± 0.691 8.19 ± 0.660 0.563

NUMBER OF STENT USED 1.07 ± 0.248 1.03 ± 0.164 0.379

VOL. OF CONTRAST USED (ML) 105.89 ± 39.50 141.57 ± 52.89 0.010

PROCEDURE DURATION (MIN) 49.27 ± 16.46 45.30 ± 13.12 0.135*

FLUOROSCOPY TIME (MIN) 14.96 ± 5.37 13.83 ± 5.17 0.253

DOSE AREA PRODUCT (μGym2) – Median (IQR)1144.700

(732.300 – 1626.800)1143.300

(653.600 – 2036.900)0.077

*Other Embolic protection device (EPD): Mo.Ma® device, SpiderFX™

**Other stents: Carotid WALLSTENT™, Acculink™ carotid stent, Advanta™ V12 Sten

VARIABLESUNIVARIATE ANALYSIS MULTIVARIATE ANALYSIS

OR (95% CI) P-VALUE OR (95% CI) P-VALUE

Age 0.97 (0.93, 1.01) 0.125 1.00 (0.94, 1.06) 0.95

Sex, Male 1.03 (0.45, 2.36) 0.941 0.93 (0.33, 2.61) 0.89

Smoking 1.94 (0.90, 4.19) 0.092 2.64 (0.90, 7.71) 0.08

Diabetes Mellitus 1.77 (0.83, 3.77) 0.138 1.31 (0.47, 3.61) 0.60

Arrhythmia 1.07 (0.42, 2.75) 0.089 1.28 (0.37, 4.47) 0.70

CAD 0.65 (0.30, 1.39) 0.265 0.66 (0.22, 1.95) 0.46

Hypertension 0.74 (0.30, 1.86) 0.529 1.05 (0.32, 3.49) 0.94

Hyperlipidemia 1.85 (0.84, 4.08) 0.127 2.15 (0.75, 6.15) 0.15

CVA 0.81 (0.25, 2.59) 0.723 1.08 (0.23, 5.00) 0.92

CRF 0.14 (0.02, 1.10) 0.062 0.10 (0.01, 1.00) 0.05

PVD 0.88 (0.42, 1.85) 0.740 1.09 (0.40, 2.97) 0.86

SBP pre-operative 0.97 (0.3, 1.00) 0.049 0.98 (0.94, 1.03) 0.42

Volume of Contrast 1.02 (1.01, 1.02) 0.0001 1.01 (1.00, 1.02) 0.048

Symptomatic vs asymptomatic 0.86 (0.41, 1.81) 0.693 0.81 (0.31, 2.14) 0.68

Arch type 0.95 (0.59, 1.53) 0.845

Degree of Carotid lesion Calcification 2.09 (1.18, 3.69) 0.010

Stent Type 0.45 (0.26, 0.78) 0.004

EPD type 1.30 (0.87, 1.93) 0.194

UNIVARIATE AND MULTIVARIATE ASSOCIATIONS BETWEEN

CLINICAL CHARACTERISTICS AND OCCURRENCE OF PPPH-CAS

EPD TYPE OR (95% CI) P-VALUE

FILTERWIRE 0.76 (0.35, 1.65) 0.49

EMBOSHIELD NAV6 0.39 (0.14, 1.10) 0.07

ANGIOGUARD 3.13 (1.45, 6.75) 0.003

Other EPD 0.35 (0.04, 2.92) 0.329

MULTIVARIATE ASSOCIATIONS EPD TYPE

AND OCCURRENCE OF PPPH-CAS

MULTIVARIATE ASSOCIATIONS STENT TYPE

AND OCCURRENCE OF PPPH-CAS

STENT TYPE OR (95% CI) P-VALUE

PRECISE PRO RX® STENT 3.71 (1.49, 9,26) 0.0006

XACT® CAROTID STENT 0.23 (0.07, 0.79 0.02

Cristallo™ Ideale 0.26 (0.06, 1.06) 0.06

Other stents 0.15 (0.01, 1.94) 0.15

PPPHCAS PREDICTION SCORING ALGORITHM USING CLINICAL CHARACTERISTICS AND STENT

PROCEDURE TYPE. RESULTS FROM MULTIVARIATE BINARY LOGISTIC REGRESSION ANALYSIS

(N=160) INCLUDING -COEFFICIENTS, ODDS RATIOS AND PPPHCAS COMPLICATION RISK

SCORE WEIGHTS.

Β coefficient OR (95% CI) p-value1

PPPH-CAS risk score

weight

Univariate C-statistic

Multivariate C-statistic

Δ C-statistic

p-value2

Age (<60 years) 1.81 6.11 (1.45, 25.7) 0.014 18 0.5549 0.5549 - -

Volume Contrast

0.6914 0.7066 0.1517 0.001

>100 0.61 1.83 (0.65, 5.17) 0.25 6

>150 1.48 4.37 (1.52, 12.54) 0.006 15

Calcification 0.6461 0.7596 0.053 0.11

2 1.07 2.93 (0.89, 9.67) 0.08 11

3 1.46 4.30 (1.10, 16.82) 0.04 15

Stent type 0.6860 0.7901 0.0305 0.26

Cordis Precise

1.31 3.71 (1.49, 9,26) 0.0006

1From multivariate binary logistic regression. 2For C-statistic : C-statistics indicate diagnostic accuracy.

PPPHCAS PREDICTION SCORING ALGORITHM USING CLINICAL CHARACTERISTICS AND STENT

PROCEDURE TYPE. RESULTS FROM MULTIVARIATE BINARY LOGISTIC REGRESSION ANALYSIS

(N=160) INCLUDING -COEFFICIENTS, ODDS RATIOS AND PPPHCAS COMPLICATION RISK

SCORE WEIGHTS.

PIVAR

DIAGNOSTIC ACCURACY FOR PPPH-CAS RISK SCORE:RECEIVER OPERATING CURVE (ROC)

0.0

00

.25

0.5

00

.75

1.0

0

Se

nsi

tivity

0.00 0.25 0.50 0.75 1.001 - Specificity

Area under ROC curve = 0.7901

The area under the ROC for the final model is 0.7901 – showing fairly good diagnostic accuracy based on our risk score.

DISTRIBUTION OF PPPH-CAS RISK SCORES AMONGST

PATIENTS WITH AND WITHOUT PPPH-CAS (N=160)

01

02

03

0

0 20 40 60 0 20 40 60

No PPPHCAS (n=123) PPPHCAS (n=37)F

req

ue

ncy

PPPHCAS risk score

This shows that a cut-point of 40 would work fairly well in terms of prediction i.e. you’re much more likely to have a complication with a score of 40+ - although there are also quite a few patients that develop complications with a lower score –

SPECIFICITY IS GOOD BUT SENSITIVITY IS NOT SO GOOD.

PREDICTED PROBABILITY OF PPPH-CAS ACCORDING TO

CALCULATED RISK SCORE (N=160)

0

20

40

60

80

100

Probability ofPPPHCAS

(%)

0 10 20 30 40 50 60 70PPPHCAS risk score

This shows there is a fairly gradual increase in risk of complications with gradually increasing risk score – rather than any very abrupt risk beyond a certain value (e.g. 40).

e.g. 40

VARIATION OF SBP

P= 0.0702 P= 0.0609P= 0.205

P= 0.2367

• 23% OF THE STUDY POPULATION DEVELOPED PHPCAS AT 30 DAYS POST-CAS.

• LOS is increased by 21% if patient develops PHPCAS [4.16±1.86 vs. 2.88

±1.84 (P < 0.01)]

• NO IMPACT ON MI. Only 1 patient had MI in the PHPCAS group vs none in

the PHPCAS group.

• NO IMPACT ON STROKE RATE: Stroke was observed in 1 patient (2.7%) with

PHPCAS vs. 3 patients (2.5%) in the no PHPCAS group.

DISCUSSION

• Patient was 4.37 times more likely to develop PHPCAS if VOLUME OF

CONTRAST WAS GREATER THAN 150ML

• STENT TYPE: 3.71 times more likely to develop PHPCAS with use of PRECISE

PRO RX® CAROTID STENT

• Two patients required pacemakers to be inserted within 72 hours

• There were no deaths at 30 days post-procedure.

DISCUSSION

• The hypothesis that remains to be proven is that an open cell stent design

conforms well with calcified anatomy and will continues to expand to the full

diameter resulting in an impact on the carotid body baroreceptor.

• The combination of Stent Design, the Degree of carotid Calcification and Contrast

Volume has predicted the occurrence of PPPH-CAS in our clinical setting.

• Our findings show that these episodes of sustained hypotension does not

translate to increased adverse clinical outcomes, including Stroke, MI and death.

CONCLUSION

B. PATRICE MWIPATAYI, MMed, FCS (SA), FRACS, GD-CLINED (Melb)

Department of Vascular Surgery, RPH

School of Surgery, University of Western Australia Perth.

Director of Perth Institute of Vascular Research (PIVAR)

PREDICTORS OF PERI-PROCEDURAL OUTCOMES OF CAS

A REAL WORLD EXPERIENCE

Rhys Daniel, MBBS, Chem.Eng

Jackie Wong, MPH