1. Renal Denervation for Non-Hypertensive Indications
Unintentional Consequences in the Evolution of Evidence and Technology
David E. Kandzari, MD, FACC, FSCAI
Chief Scientific Officer
Director, Interventional Cardiology
Piedmont Heart Institute
Atlanta, Georgia

2. David E. Kandzari, MD
Consulting: Medtronic, Inc. and Micell Technologies, Inc.
Grant Support: Boston Scientific Corporation
Honoraria: Boston Scientific Corporation
Off-Label: Use of drug eluting stents for off-label indications.

3. 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,Boston Scientific Corporation, Medtronic CardioVascular
Consulting Fees/Honoraria Abbott Vascular, Boston Scientific 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

4. Renal Sympathetic Afferent Nerves Kidney as Origin of Central Sympathetic Drive
Vasoconstriction
Atherosclerosis
Hypertrophy
Arrhythmia
Oxygen Consumption
Sleep Disturbances
Insulin
Resistance
Renal Afferent
Nerves
↑ Renin Release  RAAS activation
↑ Sodium Retention
↓ Renal Blood Flow 4 4

5. Influence of Renal Denervation on Regression of LVH and Improvement of Diastolic Function
Brandt, M. C. et al. J Am Coll Cardiol 2012;59:

6. Regression of LVH and Improvement of Diastolic Function Relative to BP Reduction Achieved by Renal Denervation
Reduction in LV mass likely result of decreased LB workload and decreased sympathetic activity
Brandt, M. C. et al. J Am Coll Cardiol 2012

7. Studies reporting safety of RND in CHF
REACH-Pilot1
Design
7 patient safety study
Chronic mod-severe heart failure
In-patient follow-up 5 day admission
Bilateral renal denervation
Aims
Safety of renal denervation
Follow-up for 6 months
Results
No procedural complications
No acute/medium term complication
Improvement in 6 min walk
OLOMOUC 12
Design
51 Randomised (OMT vs RDN)
NYHA III or IV
Bilateral renal denervation
Heart rate >70
Aims
Safety of renal denervation
Change in LV function
Results
No procedural complications
No acute/medium complication
Improvement in EF
REACH-Pilot, Davies JE, Francis DP et al. International Journal of Cardiology (ePub, October 2012)
OLOMOUC I study, ESC Munich 2012

8. Blood pressure remains stable in CHF post-denervation
REACH-Pilot, Davies JE, Francis DP et al. International Journal of Cardiology (epub online)

9. Potential Benefit of Renal Denervation in Heart Failure
Improvement in exercise capacity
REACH-Pilot
Improvement in ejection fraction
OLOMOUC I Study
Δ 27.1m
p=0.03
REACH-Pilot, Davies JE, Francis DP et al. International Journal of Cardiology (epub online)
OLOMOUC I Study, ESC 2012

10. Pulmonary Vein Isolation With or Without Concomitant RDN
No RDN
RDN
N=13
No RDN
N=14
RDN
Pokushalov et al. JACC 2012

11. Blood Pressure Variation and Obstructive Sleep Apnea

12. RDN Suppression of Postapneic Blood Pressure Increase and Atrial Fibrillation
Linz et al. Hypertension 2012

13. Change In Apena/Hypopnea Index at 3 and 6 months Following Renal Denervation
Witkowski et al. Hypertension 2011

14. RDN and Polycystic Ovarian Syndrome
PCOS: Central obesity, hyperinsulinemia and obstructive sleep apnea, are associated with chronic sympathetic overactivity1
PCOS: Increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery post-exercise1
2 HTNsive women with PCOS2
2.5 to 3 fold reduction in MSNA
17.5% increase in insulin sensitivity
Moderate reductions in blood pressure
Lansdown, Rees. Clin Endocrinol 2012
Schlaich et al. J Hypertens 2011

15. Renal Denervation Trials
Disease State
# Trials Listed
Hypertension 29
Heart Failure 6
CKD, ESRD 3
Atrial Fibrillation 2
Sleep Disordered Breathing 1
Metabolic Syndrome
Insulin Resistance
Diabetic Nephropathy
11/2012 Total 45
2/2013 Total 62

16. Renal Denervation Strategies
Device
# Trials Listed
Medtronic- (Symplicity)
Medtronic- (next generation) 29 1
Biosense Webster (ThermoCOOL) 7
St. Jude- (multi electrode basket RF)
ReCor Paradise (balloon ultrasound)
Boston Scientific-(Chilli II- EP ablation catheter)
Kona Medical-(non invasive focused ultrasound)
Marinr- (EP ablation catheter)

17. Catheter-Based Renal Denervation Opportunities for Disease Management
RDN among pts with resistant HTN is associated with
Significant and durable reductions in blood pressure
Pleiotropic effects related to hypersympathetic signature
Evolving applications in disease conditions related to hypersympathetic activity may expand therapeutic opportunities
Indication-specific trials both related to and independent of HTN are essential to clarify therapeutic potential and target patient population 17

18. Economic Impact of HTN-Related Clinical Events
Pietzsch et al. ACC 2012
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD. 18
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.

19. Economic Impact of HTN-Related Clinical Events
10 year reductions in:
Stroke %
Myocardial Infarction 32%
Coronary Heart Disease 22%
Heart Failure 21%
ESRD %
Lifetime incremental cost-effectiveness ratio (ICER) was $3,071 per quality-adjusted life-year
ICER exceeded the $50,000 per QALY willingness-to-pay threshold only when the SBP reduction after RDN was assumed to be no more than 11.1 mm Hg
Pietzsch et al. ACC 2012; Geisler JACC 2012
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD. 19
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.
Observations:
Across the spectrum of baseline SBP, RDN leads to substantial reductions in lifetime event risks.
Risk reduction for clinical outcomes tends to increase with higher baseline SBP, except for stroke and CHD.