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RDN for hypertension: Physiological rationale Dr.C.Venkata S.Ram Slide 2 Prevalence Map of Raised Lesions of Right Coronary Artery by Age and Hypertension NormotensiveHypertensiveAge 15-24 25 - 34 0-2 2-4 4-6 6-8 8-10 10+ n=1067n=185 n=1134n=233 Dr.C.Venkata S.Ram Slide 3 TEXAS BLOOD PRESSURE INSTITUTE CVD Risk Is High In RH (Redon HTN 1998;31:712) 86 Pts, 49 Months f/u CV Events = 24.6% CV Events/100 pt years 2.2 9.5 13.6 Low Tertile ADBP IntHigh Dr.C.Venkata S.Ram Slide 4 HYPERTENSION WHY INTERVENTIONAL THERAPIES ? Chronic condition Asymptomatic Complications serious Poor compliance Adverse effects: * Diuretics * blockers * CCBs * RAAS blockers * Central -agonists * Hydralazine * Minoxidil Cumulative costs Drug-drug interactions Intercurrent problems Dr.C.Venkata S.Ram Slide 5 Sympathetic Nervous System and Adrenergic Excess The autonomic nervous system and its sympathetic arm play an important role in the regulation of BP Short term regulation of BP especially in responses to transient changes in arterial BP via baroreflex mechanisms is well known Role of SNS in longer term BP regulation has been debated for many years Dr.C.Venkata S.Ram Slide 6 6 vagal efferents sympathetic efferents NE Ach EPI Stress Renal afferents Chemoreceptors Cardiac afferents NTS Baroreceptors Ang II renin NE Dr.C.Venkata S.Ram Slide 7 7 Grassi G et al., Hypertension 50:537, 2007 White Coat & Masked HTN MSNA, b / 100hb Dr.C.Venkata S.Ram Slide 8 Slide 9 Slide 10 Consequences of SNS Activation Mancia, G: http://www.sns-web.org/pdf/slideset_07.pdf Dr.C.Venkata S.Ram Slide 11 RAUWOLFIA SERPENTINA TREATMENT OF HIGH BLOOD PRESSURE BY RUSTOM JAL VAKIL ACTA MEDICA SCANDINAVICA 1955;152:107-114 Dr.C.Venkata S.Ram Slide 12 Am J Surg 75:48-68, 1948 Long Term Effect of Renal Denervation in Human Hypertension Dr.C.Venkata S.Ram Slide 13 one nerve fiber contacting multiple effectors Juxtaglomerular granular cell: renin Am J Physiol 279:R1517-1524, 2000 Renin secretion rate 1 - adrenoceptor Tubular sodium reabsorption 1B - adrenoceptor Renal blood flow 1A - adrenocepto r RSNA DiBona GF, Kopp UC. Physiol Rev 77:75-197, 1997 Effects of Renal Sympathetic Nerve Activity on Renal Function Dr.C.Venkata S.Ram Slide 14 Slide 15 Overactive SNS is Driver for Resistant HTN 10.20.2013TZeller @ TCT2013 15 G. Sangiorgi et al., TCT 2012 Significantly more nerves in hypertensive patients nerves Dr.C.Venkata S.Ram Slide 16 Renal Denervation by RF Ablation Related Changes in Underlying Physiology Office BP Renal NE spillover - left kidney - right kidney Total body NE spillover Plasma Renin Renal Plasma flow (mmHg) (ng/min) (g/l/hr) (ml/min) Baseline 161/107 72 79 600 0.3 719 1 mo 141/90 37 20 348 0.15 1126 -48% -75% -42% -50% 57% LV Mass (cMRI) dropped 7% (from 78.8 to 73.1 g/m 2 ) from baseline to 12 months Schlaich et al. NEJM. 2009; 36(9): 932-934. 17 Dr.C.Venkata S.Ram Slide 17 For distribution only in markets where the Symplicity TM renal denervation system is approved. Symplicity is a trademark of Medtronic, Inc. and is registered in one or more countries of the world. Not for distribution in the USA or Japan. 2012 Medtronic, Inc. All rights reserved. MKG025 3/12 Renal Denervation Preclinical Efficacy and Safety Extensive research in >300 swine Effectiveness: Statistically significant reduction in renal tissue NE Safety: Verification testing included angiography, gross pathology, histopathology, & clinical pathology at 7, 30, 60, and 180 days Intact endothelium by 7 days Vascular healing observed at 30 and 60 days; by 180 days, arteries were well healed (no inflammatory cells) treatment sites were considered sterile and stable No stenosis or luminal reduction seen in any treated artery through 180 days Renal Tissue NE (pg/mg) P