Renal Artery Angioplasty and Stenting: Optimal Patient Selection Ehtisham Mahmud, MD, FACC Division Chief, Cardiovascular Medicine Director, Sulpizio Cardiovascular Center-Medicine University of California, San Diego

Disclosures Clinical trial support: Corindus Consulting: Corindus, Medtronic Speakers Bureau: Medtronic, Abbott Vascular

Renal Artery Revascularization Hypertension management Renal function preservation Renal artery angioplasty -fibromuscular dysplasia -otherwise replaced by aorto-ostial stenting Renal stenting -predictors of response

Renal Fibromuscular Dysplasia: IVUS Evaluation Prasad, Mahmud et al; Cath Cardiovasc Intv 2009;74:260-4

Fibromuscular Dysplasia Mahmud et al; Catheter Cardiovasc Intv 2006; 67:434-7

Uncontrolled HTN and unilateral RAS 90% stenosis Stents back to ostia 61 year old man with uncontrolled hypertension (BP 165/100 mm Hg despite 3 antihypertensives) Mahmud et al; JACC 2007;473-90

Blood Pressure Zeller at al. Circulation 2003;108:2244-9

ASPIRE 2 Study N=208; multicenter 20 mm Hg systolic BP reduction at 12 and 24 mos Stable creatinine Restenosis: 17.4% 39% non-responders!! Rocha-Singh et al; JACC 2005; 46:776-783 Mahmud JACC 2005; 46:784-786

Blood Pressure Response in Unilateral Renal Artery Stenosis Mahmud et al; JACC Intv 2008;1:286-92 Whitlow; JACC Intv 2008;1:293-294

Renal Frame Count Control group BP>140/90 mmHg; 2 meds No renal artery stenosis Study group BP>140/90 mmHg; 2 meds Renal artery stenosis >70% Mahmud et al; JACC Intv 2008;1:286-92

Renal Frame Count Reduction Predicts Clinical Response to Renal Stenting Mahmud et al; JACC Intv 2008;1:286-92

Baseline Renal Frame Count and Blood Pressure Reduction After Renal Stenting Naghi, Mahmud et al; Cath Cardiovasc Intv 2015;86:304-309

Renal Resistive Index: Prognostic Value Radermacher J, et al. NEJM 2001;344:410-7

ASTRAL: Blood Pressure ASTRAL Investigators; NEJM 2009;361:1953-62

Randomized Trials: Major Concern STAR Bax et al; Ann Intern Med 2009:840-48 ASTRAL Astral Invest; NEJM 2009;361:1953-62

De Bruyne, B. et al. J Am Coll Cardiol 2006;48:1851-1855 Effects of a balloon-induced, unilateral, controlled, graded stenosis and renin production De Bruyne, B. et al. J Am Coll Cardiol 2006;48:1851-1855 Copyright ©2006 American College of Cardiology Foundation. Restrictions may apply.

Fractional Flow Reserve and Clinical Response to Renal Stenting Group I: FFR<0.80 Group II: FFR>0.80 N=17 Papaverine for dilation Mitchell et al; Catheter Cardiovasc Interv. 2007;69(5):685-9

Leesar, M. A. et al. J Am Coll Cardiol 2009;53:2363-2371 Representative Example of Quantitative Renal Angiography, IVUS, and TPG in a Study Patient With RAS Leesar, M. A. et al. J Am Coll Cardiol 2009;53:2363-2371 Copyright ©2009 American College of Cardiology Foundation. Restrictions may apply.

Leesar, M. A. et al. J Am Coll Cardiol 2009;53:2363-2371 Receiver-Operating Characteristic Curves of HSG, FFR, IVUS, and Diameter Stenosis for Hypertension Improvement Leesar, M. A. et al. J Am Coll Cardiol 2009;53:2363-2371 Copyright ©2009 American College of Cardiology Foundation. Restrictions may apply.

Blood Pressure Response after Renal Stenting: HSG >=21 Versus <21 mm Hg Leesar, M. A. et al. J Am Coll Cardiol 2009;53:2363-2371 Copyright ©2009 American College of Cardiology Foundation. Restrictions may apply.

Leesar, M. A. et al. J Am Coll Cardiol 2009;53:2363-2371 Number of Antihypertensive Medications and Serum Creatinine After Renal Stenting: HSG >=21 vs <21 mm Hg Leesar, M. A. et al. J Am Coll Cardiol 2009;53:2363-2371 Copyright ©2009 American College of Cardiology Foundation. Restrictions may apply.

Bilateral renal artery stenosis and renal dysfunction Stent back to ostium 99% stenosis 74 year old woman with an dysfunctional left kidney and creatinine increase from 1.9 to 4 mg/dl over two years

Stenting: Salvage Renal Function N=51 patients 42 bilateral RAS We assessed the long-term effect of successful renal artery stent revascularization on renal function, blood pressure control, and survival in patients with progressive renal dysfunction due to ischemic nephropathy. Ischemic nephropathy presents a potentially serious risk of complete loss of renal function. Surgical renal revascularization is associated with significant risk of mortality/morbidity in this patient population. The potential role and long-term effect of renal artery stent revascularization in this patient population is not well defined. A cohort of 51 patients (mean age, 72 years; 52.9% men) with progressive azotemia, defined as a preprocedure serum creatinine (Scr) value of 1.5 mg/dl and a negative slope of the reciprocal 1/Scr curve during the 12 months preceding revascularization, underwent successful primary stent deployment in 93 atherosclerotic renal artery lesions (42 bilateral, 9 solitary kidneys). Estimated glomerular filtration rate (EGFR) and serum creatinine values, blood pressure, antihypertensive medication requirements, and survival rates were monitored over a mean of 30-month follow-up. Renal artery duplex Doppler or renal angiography were performed at a mean of 13 months (range, 7-15 months) to assess stent patency. Stent implantation was successful in 92/93 (98.9%) stenotic renal arteries (mean preprocedure serum creatinine 2.3 ± 0.9 mg/dl; range, 1.5-8.2 mg/dl). Forty-seven patients were eligible for 30-month follow-up of the procedural effect on renal function, blood pressure control, number of antihypertensive medications, and survival. At 1-year follow-up, the slope of the 1/Scr curve increased and the EGFR values significantly improved compared to preprocedure values (19.9 ± 6.2 to 26.8 ± 10.1 ml/min; P < 0.0001), serum creatinine decreased from the mean preprocedure value to 1.75 ± 0.69 mg/dl (P < 0.001), with renal function improvement or stabilization observed in 94% of patients; three patients (7.3%) required permanent hemodialysis during the 30-month follow-up period. Systolic and diastolic blood pressure significantly decreased (from 177 ± 28 to 148 ± 25 mm Hg and from 92 ± 15 to 78 ± 14 mm Hg, respectively; P < 0.001) with fewer antihypertensive medications required to control blood pressure (3.5 ± 0.9 vs. 1.9 ± 1.3; P < 0.001). The patient survival rate after 30-month follow-up was 87%, with three deaths related to end-stage renal failure. Renal artery stent revascularization reversed progressive renal dysfunction within the first 12 months and maintained the improved level of renal function at 30-month follow-up while improving blood pressure control and reducing the number of antihypertensive medication requirements. Renal stent revascularization should be considered a valid therapeutic option for the long-term treatment of ischemic nephropathy. Cathet Cardiovasc Intervent 2002;57:135-141. Rocha-Singh et al; Cath Cardio Interv 2002;57:135-41

Renal Artery Stenosis: Clinical Indications for treatment (clinical presentation): Renovascular hypertension (BP ≥140/90 mm Hg; ≥2 antihypertensives) especially young or new onset elderly Ambulatory BP monitoring rather than single measurement Progressive, accelerated renal insufficiency Recurrent/flash pulmonary edema Global renal ischemia Renovascular Hypertension: correction of a stenosis > 50%, resting pressure gradient >10mm Hg or occlusion that is associated with refractory hypertension or documentation of renovascular hypertension Renal Insufficiency: Deterioration of renal function of asymmetric decrease in renal size, and renal artery stenosis >50% Recurrent PE: due to bilateral renal artery stenosis

Renal Artery Stenosis: Markers of Success Anatomical features: Kidney >8 cm Angiographic diameter stenosis >70% by QRA IVUS CSA stenosis >80% Physiological measures: Resistive index <0.80 Mean Pd:Pa <0.80 (renal FFR) Hyperemic systolic gradient ≥ 21 mm Hg Increased baseline renal frame count (>30) and RBG≥1 Novel measures: Decreased RFC after renal stenting Biomarkers/New Imaging: BNP, renal penumbra Renovascular Hypertension: correction of a stenosis > 50%, resting pressure gradient >10mm Hg or occlusion that is associated with refractory hypertension or documentation of renovascular hypertension Renal Insufficiency: Deterioration of renal function of asymmetric decrease in renal size, and renal artery stenosis >50% Recurrent PE: due to bilateral renal artery stenosis

Renal Artery Stenosis: Markers of Success Anatomical features: Kidney >8 cm Angiographic diameter stenosis >70% by QRA IVUS CSA stenosis >80% Physiological measures: Resistive index <0.80 Mean Pd:Pa <0.80 (renal FFR) Hyperemic systolic gradient ≥ 21 mm Hg Increased baseline renal frame count (>30) and RBG≥1 Novel measures: Decreased RFC after renal stenting Biomarkers/New Imaging: BNP, renal penumbra Renovascular Hypertension: correction of a stenosis > 50%, resting pressure gradient >10mm Hg or occlusion that is associated with refractory hypertension or documentation of renovascular hypertension Renal Insufficiency: Deterioration of renal function of asymmetric decrease in renal size, and renal artery stenosis >50% Recurrent PE: due to bilateral renal artery stenosis

Renal Artery Stenosis: Markers of Success Anatomical features: Kidney >8 cm Angiographic diameter stenosis >70% by QRA IVUS CSA stenosis >80% Physiological measures: Resistive index <0.80 Mean Pd:Pa <0.80 (renal FFR) Hyperemic systolic gradient ≥ 21 mm Hg Increased baseline renal frame count (>30) and RBG≥1 Novel measures: Decreased RFC after renal stenting Biomarkers/New Imaging: BNP, renal penumbra Renovascular Hypertension: correction of a stenosis > 50%, resting pressure gradient >10mm Hg or occlusion that is associated with refractory hypertension or documentation of renovascular hypertension Renal Insufficiency: Deterioration of renal function of asymmetric decrease in renal size, and renal artery stenosis >50% Recurrent PE: due to bilateral renal artery stenosis