Verify the efficacy of renal artery stenting to define the predictive factors by physiological

assessment with pressure wire gradientVERDICT study

Masahiko Fujihara, MDKishiwada Tokushukai Hospital

Osaka, Japan

Disclosure

Speaker name :

Mashiko Fujihara

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

STAR, ASTRAL and CORAL trialshowed NO benefit in the preservation of renal function, cardiovascular events and reduce blood pressure when compared with optimal medical therapy

BACK GROUND of Renal Artery Stenting

Bax L et al. STAR trial. Ann Intern Med 2009; 150: 840–848, W150–W151.Wheatley K et al. N Engl J Med 2009; 361: 1953–1962.Cooper CJ, et al. N Engl J Med 2014; 370: 13–22.

From Latest guideline (ESC 2017)

2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS) European Heart Journal (2017)

Renal revascularization does not generally improve blood pressure,renal or CV outcomes in patients with atherosclerotic RAD.

With the low evidence of a potential benefit for revascularizationover medical therapy

Post ASTRAL and CORAL era- How do we indicate renal stent ? -

• Significant RAS should be indicated with apparent clinical manifestation of ARAS

• Negative results of large RCTs posed difficulties in selecting the treatment strategy for ARAS

• Renal stent may not be effective in all cases, but there are responder for renal revascularization that might give impact on resistant hypertension

Define the Predictor

Patient Characteristic Character

Rapid worsening of renal function

BNP> 80 or 50 pg/dl No albuminuria

• Zeller T, et al. Circulation 4;108(18):2244-9,2003• Muray S, et al. Am J Kidney Dis 39(1):60-6, 2002 • Davies MG, et al. J Vasc Surg 51(5):1222-9,2010 • Cianci R,et al. Ren Fail 32(10):1167-71, 2010• Silva JA, et al. Circulation 25;111(3):328-33.2005• Staub D, et al. Eur J Vasc Endovasc Surg 40(5):599-

607.2010

Lesion Characteristic

Resistance Index (RI) Pressure Gradient Pd/Pa (Rest) Renal FFR=Pd/Pa (Stress)

• Santos S, et al. Arq Bras Cardiol 94(4):452-6, 2010 • Massound A, et al. J Am Cardiol 53:2263,2009• Fabio Mangiacapra et al, Circulation 3;537-, 2010• Marcin Protasiewicz et al, Am J Cardiol. 112:2013• Mitchell et al : CCI 69:685-689, 2007• Berbard Bruyne et al, JACC 48;1851-1855, 2006

Procedure Characteristics

Embolic Distal Protection(Angiogurard)+abciximab

• Christopher J. Cooper et al. (Circulation 117:2752-2760. 2008

Study Design

A prospective, multicenter, single-arm clinical study of patients with significant RAS with hypertension and/or CKD (UMIN000010109)

Treated System

the Express SD stent system (Boston Scientific)the Aeris/Certus pressure wire (St Jude Medical)

Primary Endpoint

Define the prediction factors that reduced blood pressure in the HTN group, and improved renal function in the CKD group

Patients / Centers

221 patients/ 32 centers

DESIGN and ENDPOINTS

VERDICT Study Scheme

2 cases were excluded for lack of primary data

7 cases were excluded for protocol violation

221 patients Enrolled in this study

212 patients Primary analysis (Basic Characteristics)

193 patients Hypertension group

164 patients CKD group

200 patients Primary analysis (9 months)

183 patients Hypertension group

VERDICT Procedural Scheme

ClinicalIndication

Diagnosisof

ARASSignificant RAS

Renal Artery

Stenting

PrimaryEvaluation9months

SBP: ≥ 145mmHg(Office)and≥ 135mmHg(24hABPM)with 3≥medicine

De novo:Duplex: PSV≥219cm/s and RAR≥3.5

→PSV<219cm/sRAR<3.5Excluded

Angiography:%DS>60%physiologicalassessment:Pressure Gradient≥20mmHg(Rest/Stress)→<20mmHgExcluded

Stent:physiologicalassessment:(Post)

PGPd/PsRenal FFRRenal Flow Reserve

SBP:(Office/24h)Office/24hDUS:

Responder

NonResponder

Age (years old) 73.7 Office BP SBP (mmHg) 151.6

Male (%) 76.6 Office BP DBP (mmHg) 77.7

Diabetes (%) 45.6 24H ABPM SBP (mmHg) 149.6

CKD (%) 77.5 24H ABPM DBP (mmHg) 76.9

Dyslipidemia (%) 73.0 24 Hours Blood Pressure Pattern

Obesity(%) BMI>25 22.2 -Dipper (%) 42 (25.9)

Current Smoking (%) 23.3 -Extreme Dipper (%) 7 (4.3)

Heart Failure (%) 26.4 -Non Dipper (%) 67 (41.4)

Antihypertensive medicine 2.8±1.3 -Riser (%) 49 (30.2)

Ejection Fraction (%) 63.3

Patient Characteristics (N=193)

Duplex findings

Kidney size (cm) 9.7

PSV (cm/s) 321.1

RAR 5.07

RI 0.74

Physiological Assessment by pressure wire

Rest PG (SYS) mmHg 32.8

Rest Pd/Pa (SYS) 0.79

Stress PG (SYS) mmHg 47.6

Stress Pd/Pa (SYS) =Renal FFR 0.69

Rest PG (MEAN) mmHg 12.0

Stress PG (MEAN) mmHg 18.1

Renal Flow Reserve (√StressPG(Mean)/√RestPG(Mean)) 1.3

Treated Lesion Characteristics (N=193)

Clinical Responder Rate in hypertension

Responder;OBP>10 mmHg SBP reduction (Pre SBP 150～180mmHg)OBP>15 mmHg SBP reduction (Pre SBP >180mmHg)24HABPM> 20mmHg SBP reductionat 9 months

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

OBP 24HABPM

Responser Non responder

Responder

61%

Responder

63%

Non Responder39%

Non Responder37%

The predictive factors of clinical responder

Responder (Office BP) Responder ABPM

p OR 95%CI p OR 95%CI

Age 0.843 1.00 0.95 1.04 0.787 1.01 0.96 1.06

Male 0.163 0.52 0.21 1.30 0.981 1.01 0.41 2.47

Dyslipidemia 0.091 0.32 0.09 1.20 0.107 0.28 0.06 1.32

Diabetes 0.567 0.81 0.38 1.69 0.075 0.50 0.23 1.07

CKD 0.169 0.51 0.20 1.33 0.643 0.81 0.34 1.95

Cr 0.025* 0.37 0.16 0.89 0.874 0.94 0.43 2.04

CAD 0.002* 0.25 0.11 0.59 0.053 0.45 0.20 1.01

Heart Failure 0.263 1.66 0.68 4.03 0.092 0.45 0.18 1.14

BNP 0.926 1.00 1.00 1.00 0.455 1.00 1.00 1.00

Calcium channel blocker 0.633 0.80 0.32 1.99 0.603 1.31 0.48 3.56

ARB/ACEi 0.112 0.50 0.22 1.17 0.105 0.48 0.20 1.16

Diuretics 0.002* 3.79 1.60 8.96 0.002* 4.80 1.80 12.81

The number of AHM 0.482 1.11 0.83 1.47 0.876 1.03 0.76 1.39

Statin 0.434 0.73 0.34 1.59 0.553 0.79 0.35 1.74

The predictive factors of clinical responder

Responder (Office BP) Responder ABPM

p OR 95%CI p OR 95%CI

Baseline Office blood pressure 0.000* 1.08 1.04 1.11 0.178 0.99 0.97 1.01

Baseline 24HABPM 0.095 1.03 1.00 1.06 0.001* 1.07 1.03 1.11

(DUPLEX) PSV 0.442 1.00 0.99 1.00 0.742 1.00 1.00 1.01

(DUPLEX) RAR 0.903 1.01 0.83 1.23 0.733 1.04 0.84 1.28

(DUPLEX) RI 0.879 1.33 0.03 54.25 0.788 0.59 0.01 28.92

Bilateral treatment 0.497 0.69 0.23 2.04 0.385 1.71 0.51 5.77

Contrast media doze 0.161 1.01 1.00 1.02 0.521 1.00 0.99 1.01

% stenosis 0.119 0.97 0.94 1.01 0.592 0.99 0.96 1.03

Stent diameter 0.402 0.76 0.39 1.46 0.866 1.06 0.54 2.06

Stent diameter 0.402 0.76 0.39 1.46 0.866 1.06 0.54 2.06

IVUS usage 0.422 1.41 0.61 3.23 0.350 1.49 0.65 3.44

Distal protection 0.094 0.50 0.22 1.12 0.663 0.83 0.36 1.90

The predictive factors of clinical responder-physiological assessment-

Responder (Office BP) Responder ABPM

p OR 95%CI p OR 95%CI

Sys PG（Rest） 0.184 0.99 0.97 1.01 0.789 1.00 0.99 1.02

Sys Pd/Pa（Rest） 0.416 3.64 0.16 82.41 0.439 0.30 0.01 6.47

Mean PG(Rest) 0.787 1.00 0.96 1.03 0.765 1.01 0.97 1.04

Mean Pd/Pa (Rest) 0.812 0.64 0.02 25.66 0.672 0.46 0.01 17.43

Sys PG(Stress) 0.052 0.98 0.97 1.00 0.974 1.00 0.99 1.02

Sys Pd/Pa（Stress） 0.177 7.41 0.41 135.41 0.630 0.50 0.03 8.14

Mean PG(Stress) 0.272 0.99 0.96 1.01 0.869 1.00 0.97 1.03

Renal FFR*1 0.459 3.04 0.16 57.86 0.901 0.83 0.04 15.80

Renal Flow Reserve*2 0.790 0.91 0.44 1.87 0.832 1.09 0.51 2.30

Sys PG(Post Stress) 0.905 1.00 0.95 1.07 0.140 1.05 0.98 1.13

Mean PG (Post Stress) 0.312 1.05 0.95 1.16 0.047* 1.20 1.00 1.44

*1 Renal FFR; Stress Pd/Pa (SYS) *2 Renal Flow reserve √StressPG(Mean)/√RestPG(Mean))

Conclusion

• VERDICT study focuses on selecting patients who have hemodynamically proven renal hypo-perfusion with significantly ARAS.

• The indicated significant renal artery stenosis patients got a better response 60% of hypertension

• This study gave us some predictive factors for clinical response

• Otherwise, physiological assessment of ARAS using pressure wire did not predict the clinical response after renal artery stenting, non-similar to the coronary FFR studies.

Thank you for your attention

JET2018 Osaka, Japan

February 23(Fri)-25(Sun) 201810th Anniversary JET 2018