Transcript renal denervation WIN2011 Abbott

Radial Frequency Ablation for
Hypertension Treatment: Help or
Hype?
J. Dawn Abbott, M.D., F.A.C.C., F.S.C.A.I.
Director, Interventional Cardiology Fellowship
Assistant Professor of Medicine
Brown Medical School
Division of Cardiology, Rhode Island Hospital
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-Investigational Devices
Arterial Hypertension
 Most frequent cause of death worldwide
 20mmHg increase in BP doubles cardiovascular mortality
 > 80% of patients with arterial hypertension are not treated
adequately or can not be treated adequately
 20-30% of patients with HTN have or will develop
resistant HTN
• Resistant HTN-failure to achieve goal BP (140/90, 130/80
DM/CKD) when adhering to maximally tolerated doses of 3 drugs
including a diuretic.
 Reduction of systolic blood pressure by 10 mmHg reduces
the risk of stroke by 30%
Role of Kidney in Blood Pressure
Regulation
 The kidney plays a pivotal role in BP
regulation through sodium, volume, renin
modulation, and renal-sympathetic neuronal
interactions.
 Renal sympathetic efferent and afferent
nerves contribute to the pathogenesis of
hypertension.
Regulators of Renal Efferent Nerves
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Central sympathetic nervous system
Aortic and carotid baroreflexes
Cardiac stretch receptors with vagal afferents
Renorenal reflexes that alter the level of efferent nerve
activity in the contralateral kidney
 Kidney is the recipient of sympathetic signals via the renal
efferent nerves
• Increases renin release
– Activation of RAAS system
• Increases sodium retention
• Decreases Renal blood flow
Essential HTN and CKD
Vasoconstriction
Arteriosclerosis
Renal Afferent
Nerves
Insulin resistance
Renin- release
NaCL-retention
Renal blood flow
Hypertrophy
Arrhythmia
O2 consumption
Heart failure
Early Proof of Concept Studies
Sympathectomy in Hypertension
Mortality benefit at the expense of side effects
Smithwick RH, J Am Med Assoc. 1953;152:1501-1504
Selective Renal Sympathetic
Denervation: Therapeutic Target.
 Preclinical studies catheter
based RFA main renal
artery
• reduces noradrenaline
content in the kidney by
more than 85%
• comparable to direct
surgical renal denervation
via artery transection and
re-anastomosis.
• No severe vascular or renal
injury at 6 months
The Catheter System
Symplicity by Ardian Inc, Palo Alto, CA, USA*
 6F compatible, articulating
tip RF electrode
 Energy maximum 8 Watt
 Energy application up to 5x
for each renal artery,
depending on length
 2 minutes per energy
application
*Investigational Device. Limited by U.S. law to investigational use.
Case Example of RFA Application
Clinical Data
Initial Cohort
 First-in-man, non-randomized
 Cohort of 45 patients with resistant HTN (SBP
≥160 mmHg on ≥3 anti-HTN drugs, including a
diuretic; eGFR ≥ 45 mL/min)
 Mean age 58, 44% female, 32% DM, 22% CAD
 Mean antihypertensive drugs 4.7
 12-month data
 Subgroup - NE spillover reduced 47%
 5 pts unsuitable anatomy
Lancet. 2009;373:1275-1281
Change in Office BP
Lancet. 2009;373:1275-1281
Symplicity HTN-1: Expanded
Cohort and Follow-up
(n=153)
Sievert et al. European Society of Cardiology 2010.
Procedural Specifics and Safety
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38 minute median procedure time
Average of 4 ablations per artery
IV narcotics & sedatives for pain
No catheter or generator malfunctions Complications
• 1 renal artery dissection from catheter
• 3 access site
 81 patients with 6-month renal CTA, MRA, or Duplex
• No vascular abnormalities at any site of RF delivery
• One progression of a pre-existing stenosis
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Two deaths within the follow-up period unrelated to the device or
therapy
 No orthostatic or electrolyte disturbances
 No change in renal function (Δ eGFR)
Transient vasospasm
 Randomized, controlled, clinical trial
 106 patients randomized 1:1 to treatment with renal denervation vs.
control
 24 centers in Europe, Australia, & New Zealand
 Inclusion Criteria:
• Office SBP ≥ 160 mmHg (≥ 150 mmHg with type II diabetes mellitus) ≥3
anti-HTN medications
 Exclusion Criteria:
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Significant renal artery abnormalities/prior renal artery intervention
eGFR < 45 mL/min/1.73m2 (MDRD formula)
Type 1 diabetes mellitus
Contraindication to MRI
Stenotic valvular heart disease
MI, unstable angina, or CVA in the prior 6 months
Lancet. 2010;376:1903-1909
Trial Profile
Lancet. 2010;376:1903-1909
Primary Endpoint: 6-Month Office BP
• 84% of RDN patients had ≥ 10 mmHg reduction in SBP (vs 35% controls)
• 10% of RDN patients had no reduction in SBP
BP Distribution in RDN and
Controls at 6 Months
>180
160-179
140-159
<140
Additional BP Outcome Measures
Conditions Likely to Respond to
Renal Denervation
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Resistant essential hypertension
Essential hypertension intolerant to medications
Nondipping essential hypertension
Resistant renovascular hypertension
Hypertension with chronic renal disease (unilateral or bilateral)
Hypertension with obstructive sleep apnea intolerant to continuous
positive airway pressure
 Congestive heart failure (with reduced or preserved left ventricular
systolic function) with cardiorenal syndrome
 Hypertension in end-stage kidney disease on dialysis with native
kidneys
 Hypertension in renal transplant patients with remaining native
kidneys
Potential Long-term Benefits of
Renal Denervation
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Attenuation of arterial pressure*
Attenuation of arterial pressure during exercise*
Stabilization of renal function with attenuation of the rate of decline of
estimated glomerular filtration rate and reduction of proteinuria in
hypertensive patients
Restoration of nocturnal dipping*
Regression of left ventricular hypertrophy
Decreased insulin resistance*
Slower progression of vascular disease
Decreased incidence of congestive heart failure with reduced ventricular
hypertrophy, reduced salt and water retention, and improved exercise tolerance
Decreased risk of stroke
Decreased risk of atrial and ventricular arrhythmias
Decreased risk of sudden cardiac death
* Demonstrated in clinical trials
Cardiorespiratory Response to
Exercise After RSD
 46 patients with therapy-resistant hypertension in
Symplicity HTN-2
 Cardiopulmonary exercise tests were performed at
baseline and 3-month follow-up
 RSD reduces blood pressure during exercise
without compromising chronotropic competence
 Heart rate at rest decreased and heart rate recovery
improved after the procedure
Changes in BP with Exercise
Ukena, C. et al. J Am Coll Cardiol 2011;58:1176-1182
Renal Denervation and Insulin Resistance
 Bidirectional relationship
between sympathetic
overactivity and insulin
resistance and
hyperinsulinemia
producing sympathetic
activation
 Renal denervation
improves glucose
metabolism and insulin
sensitivity
fasting glucose (A), fasting insulin (B), C-peptide (C), and homeostasis model assessment–insulin
resistance (HOMA-IR; D)
Conclusions
 Catheter based renal renervation results in
significant reductions in BP
 The therapy appears safe out to 2 years
 The magnitude of BP reduction should
reduce the risk of HTN related morbidity
and mortality
 Secondary benefits deserve further study