Opportunities for Intervention Emerging Indications for Endovascular Treatment: Erectile Dysfunction David E. Kandzari, MD, FACC, FSCAI david.kandzari@piedmont.org Director, Interventional Cardiology, Piedmont Heart Institute Chief Scientific Officer, Piedmont Healthcare Atlanta, Georgia

Disclosure Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below Affiliation/Financial Relationship Company Grant/Research Support Abbott Vascular, Cordis Corporation, Medtronic CardioVascular Consulting Fees/Honoraria Abbott Vascular, Cordis Corporation, Medtronic CardioVascular, Micell Technologies, Terumo Medical Major Stock Shareholder/Equity None Royalty Income None Ownership/Founder None Intellectual Property Rights None Other Financial Benefit None

Erectile Dysfunction and Vascular Risk Frequency and Implications ED independently predicts cardiovascular disease1 ~40% increased risk Development of ED predates the onset of symptomatic cardiovascular atherosclerotic disease by 3-5 years2 ED predictive of All cause mortality3 Cardiovascular death/MI/stroke/heart failure3 At least as predictive as smoking history or family history for premature CAD4 Up to 70% of men with CAD have ED5 Association with CAD6 More likely to be sexually inactive (31% vs 0) Greater ED prevalence among sexually active (86% vs 73%) 1Araujo et al. JACC 2010; 2Thompson et al. JAMA 2005; 3Bohm et al. Circulation 2010; 4Chiurlia et al. JACC 2005; 5Rogers et al PANPI TCT2009; 6Justo et al. Int Impotence Res 2010 3

Erectile Dysfunction 80% of ED has a vasculogenic etiology1 ED is associated with substantially reduced quality of life for both the patient and partner2 Treatments directed toward underlying pathophysiology are limited, particularly for advanced disease Treatment Severity PDE 5i Oral Therapy IC Penile Injection Intra-urethral Suppository Vacuum Pump Penile Prosthesis Sildenafil (Viagra, Pfizer) Vardenafil (Levitra, Bayer) Tadalafil (Cialis, Lilly) 1Lue. NEJM 2000; Goldstein et al. 2J Sex Med 2005 4

Erectile Dysfunction and Vascular Risk Frequency and Implications “Up to 2.5 million men in Western Europe are exposed to illicit sildenafil…” “Among men with ED purchasing non-prescription ED drugs, 67% do so over the Internet and the proportion of these counterfeit drugs are estimated 44% to 90%.” “Inconsistent doses of active pharmaceutical ingredient range from 0 to >200% of labelled dose, contaminants including talcum powder, commercial paint and printer ink...” 5

Erectile Dysfunction and Vascular Etiology Non-Invasive Assessment Erectile Function Domain Scores Sexual Encounter Profile (SEP) International Index of Erectile Function (IIEF) 6

Erectile Dysfunction and Vascular Etiology Non-Invasive Assessment Erectile Function Domain Scores Sexual Encounter Profile (SEP) International Index of Erectile Function (IIEF) Intracavernosal Injection and Duplex Ultrasound Gray scale studies assess: Corporal Fibrosis Grade 1-3 Caversnosal Atherosclerosis Grade 1-3 7

Erectile Dysfunction and Vascular Etiology Non-Invasive Assessment Erectile Function Domain Scores Sexual Encounter Profile (SEP) International Index of Erectile Function (IIEF) Intracavernosal Injection and Duplex Ultrasound Gray scale studies assess coporal fibrosis and cavernosal atherosclerosis Peak systolic flow velocities to assess cavernosal artery insufficiency End diastolic velocities to assess corporal veno-occlusive capacity 8

Erectile Dysfunction and Vascular Etiology Duplex Ultrasound “Normal Inflow, No Leak” “Abnormal Inflow, Leak” Left Cavernosal PSV 31.9 cm/s EDV 0 cm/s Right Cavernosal PSV 15.9 cm/s EDV 7.5 cm/s 9

Feasibility of Percutaneous Revascularization with DES for Erectile Dysfunction Cavernosal arteries fed by the internal pudendal artery (IPA) IPA caliber 2.5-2.5 mm Non-tortuous, relatively easy access ZEN: FIM trial for PDE-5 inhibitor resistant patients Angiogram of IPA Stenoses

Erectile Dysfunction and Vascular Etiology Angiography 38 RCTs 18,000 pts

Erectile Dysfunction and Vascular Etiology Angiography 38 RCTs 18,000 pts

Selective Left Internal Pudendal Angiography 38 RCTs 18,000 pts

Pudendal Angiography, IVUS and OCT Insights From Imaging 38 RCTs 18,000 pts

Pudendal Angiography, IVUS and OCT Insights From Imaging 38 RCTs 18,000 pts

Selective Right Internal Pudendal Angiography (Normal) Case 1: 43yo with Cholesterol, Smoker, HTN, Family History for Early CAD Selective Right Internal Pudendal Angiography (Normal) 38 RCTs 18,000 pts

Case 1 Left Internal Pudendal Artery Stenosis 38 RCTs 18,000 pts

Case 1 Pre-Dilation and Stent Deployment Stent Deployment 38 RCTs 18,000 pts Stent Deployment 2.5X30 mm DES Pre-Dilation

Case 1 Final Result 38 RCTs 18,000 pts

Case 1 Final Result: No Distortion with Hip Flexion 38 RCTs 18,000 pts

65yo with HTN, Cholesterol Selective Right IPA Angiogram 38 RCTs 18,000 pts

Case 2 Predilation and Stent Delivery 2.75X30 mm DES

Case 2 Left IPA Non-Selective Angiogram 38 RCTs 18,000 pts

Case 2 Left IPA: Final Result 38 RCTs 18,000 pts

Case 2 Objective Assessment: 30 Day Ultrasound Pre-procedure Post-procedure Left CA: PSV 10.4 cm/sec; EDV 3.0 cm/sec; RI 3.5 Left CA: PSV 31.9 cm/sec; EDV 0 cm/sec; RI 31.9

Lessons Learned in Early Experience with PPI PercutaneousPudendal Intervention 38 RCTs 18,000 pts PPI is feasible and may be achieved with existing catheter-based technologies and technique Enrollment screening presents unique challenges and opportunities for patient and health care provider education Despite rigorous run-in screening for apparently eligible patients, not all patients may be appropriate, highlighting opportunities for enhanced noninvasive assessment Early experience with ZEN introduces potential to inform ED physiology, predictors of outcome and risk stratification With appropriate patient selection, PPI is associated with promising early clinical success