1. Device Therapy Paul A. Sobotka, MD Professor of Medicine/Cardiology
The Ohio State University
Chief Medical Officer
Cibiem, Inc.

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Consulting Fees/Honoraria
Royalty Income
Ownership/Founder/Salary
Ardelyx Inc.
Medtronic, Inc.
Rox Medical, Inc.
Ardian, Inc.
Cibiem, Inc.

3. Renal denervation in less severe treatment resistant hypertension
Christian Ott, Felix Mahfoud, Axel Schmid, Tilmann Ditting, Paul A. Sobotka, Roland Veelken, Aline Spies, Christian Ukena, Ulrich Laufs, Michael Uder, Michael Bohm, Roland E. Schmieder
Submitted
Embargoed

4. Moderate Hypertension
Device therapy for the treatment of hypertension which is NOT proved unresponsive to diet, exercise and medications
Device therapy enabling treatment of the persistently non compliant patient
Device therapy as an empowering choice for patients to select between treatment with a device and life long poly pharmacy

5. Background Drug Therapy
Proof of safety and efficacy requires stationary background diet, exercise, and drug therapy
Resistant hypertension
Defines a subgroup of HTN patients who may derive benefit from device intervention
In the opinion of many HTN experts, device therapy should be reserved for compliant patients who accept life long poly pharmacy as a treatment strategy and whose physicians are expert in using highest doses of several drugs used in combinations untested and unproven safe and effective

6. rHTN- Patient Selection?
What constitutes failed pharma therapy?
3 drugs, maximal doses (one being a diuretic)?
3 drugs, maximal doses (one being a diuretic), one being spironolactone?
Care provided by an HTN expert?
Does patient choice matter?
Does willful non-compliance with life long poly pharmacy recuse patients from consideration?

7. Blood Pressure is a lousy way of measuring hypertension
Blood pressure is the product of cardiac output, vascular capacitance, compliance, reflection and resistance
MI can cure high blood pressure but not hypertension
Blood pressure is dynamic; a single measure cannot adequately characterize vascular dynamics when at rest and when under stress.

8. BP Syndromes Hypertension (mild, moderate, severe)
White coat hypertension (hypertension only when in the physicians office)
Concealed hypertension (hypertension only when at home)
Episodic hypertension (malignant, crisis)
Pseudo hypertension (something to do with patient behaviors, or clinical failure to properly measure)

9. Special case of untreatable hypertension
New and novel devices must demonstrate safety and define effectiveness to inform patient choice
Special case of untreatable hypertension
Above target despite diet/exercise/medication compliance
To reduce calculated 10 year CV risk
To attenuate or reverse end organ damage
Special case of the persistently non compliant patient
Universal case of empowering patient choice

10. Moderate vs Severe HTN
The CV risk of hypertension is linear for all bp above 140mmHg
Restricting therapy to those with ULTRA hypertension (>160 mmHg) versus those with Moderate ( mmHg) is indefensible
A 20 mmHg reduction of bp generates same benefit for a patient with ultra and with moderate hypertension
A 20 mmHg reduction of bp attains infinite individual and social benefit for the non compliant patient

11. Risk:Benefit Device Therapy HTN
Symptom
reduction
Prevention
Mortality reduction
Risk of native disease

12. Risk:Benefit Device Therapy HTN
Symptom
reduction
Prevention
Mortality reduction
MHTN
SHTN
rHTN
Afib
CKD
CHF
Risk of native disease

13. Risk:Benefit Device Therapy HTN
Symptom
reduction
Prevention
Mortality reduction
CHF
CKD
Afib
Magnitude of benefit
SHTN
rHTN
MHTN
Risk of native disease
Resistant could be either moderate or severe

14. Risk:Benefit Device Therapy HTN
Symptom
reduction
Prevention
Mortality reduction
CHF
Afib
Magnitude of benefit
SHTN
rHTN
CKD
MHTN
Risk of native disease
Inherent Procedure
Risk
ADD SPHERES instead of circles
The benefit is related to the biologic limits of improvements:
A patient with 180mmHg baseline can experience a 40 mmHg reduction
A patient with a 160mmHg baseline can experience only a 20 mmHg improvement

15. Vascular and Renal Safety
Vascular Safety
Acute Renal Artery structure and function
Preclinical: structural integrity of artery
Human: post procedure arterial imaging
Chronic Renal Artery structure and function
Preclinical: 3 month pig anatomy and histology
Human: 6 month follow up demonstration of patency and lack of therapy related aneurysms, or clinically important stenosis
Renal Safety
Human: serial tracking of changes in kidney function relative to adequate control population (eGFR can hide mischief )

16. Clinical Endpoints Hypertension Non Hypertension
Refractory, resistant, difficult to treat, moderate, patient preference (non compliance)
Non Hypertension
HFrEF, HFpEF, prevention or treatment of tachy atrial or ventricular arrhythmias, ADHF, prevention of CKD progression, SDB (central, obstructive), insulin resistance…..

17. Terminal Thoughts A final cautionary thought.
I’ve been traveling through a lot of airline terminals lately. Here’s a diagram of several of them.
Most people looking at this diagram will conclude there are many ways to build an airport.
But I’m more cynical. I think it means we haven’t yet learned how to build one!