1. Potential conflicts of interest
Speaker’s name: Pekarskiy
 I have the following potential conflicts of interest to report:
 Research contracts  Consulting
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
 Other(s)
 I do not have any potential conflict of interest X

2. Radiofrequency Renal Denervation For Resistant Hypertension: Single Institution Efficacy And Safety Study
PEKARSKIY S., VARVARENKO V., VINTIZENKO S., RIPP T., SEMKE G., MORDOVIN V., KRYLOV A., POPOV S.
Research Institute of Сardiology, Siberian Branch of the Russian Academy of Medical Sciences
TOMSK, RUSSIAN FEDERATION

3. Tomsk Research Institute Of Cardiology
is a large governmental research center with 430-bed hospital providing a full spectrum of cardiac services, including
emergency care,
diagnostic,
interventional cardiology,
cardiac surgery and rehabilitation
to residents of Siberia and Eastern Russia
patients annually
Full array of diagnostic capabilities(CT, MRI, ultrasound, nuclear imaging, biopsy etc)
Cath lab with 3 OR providing all kinds of coronary, peripheral, congenital and structural interventions
50-bed dedicated hypertension unit annually provides advanced investigation and treatment to more than 1000 patients with hard- to-control hypertension
Largest research institution in the region of Siberia and Eastern Russia with license and expertise to perform all kinds of pre-clinical and clinical research including pre-approval clinical trials of new therapies and devices
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4. Our Study
Single-center Single-arm Study Of The Efficacy And Safety Of Radiofrequency Sympathetic Renal Denervation For Treatment Of Drug Resistant Hypertension (ClinicalTrials.gov Identifier: NCT ).
Inclusion Criteria:
Age ≥ 18 and ≤ 80 years at the time of randomization
Informed consent
Treatment with full doses of 3 or more anti-hypertensive medications of different classes, of which one is a diuretic.
Office Systolic BP (SBP) ≥ 160 mmHg or Diastolic BP (DBP) ≥ 100 mmHg
Exclusion Criteria:
An estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73 m2
(ABPM) 24 hour average SBP < 135 mmHg
Symptomatic(secondary) hypertension
Severe renal artery stenosis or abnormality
Pregnancy, nursing
Any other clinically important disorders or dysfunctions preventing study participation (investigator's assessment)
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5. Safety endpoints Efficacy endpoints
Primary:
Number of Serious Adverse Events related to the intervention from baseline to 12 months
Secondary:
Change in serum creatinine from baseline to 1 week, 6 and 12 months
Change of protein concentration in morning urine sample from baseline to 1 week, 6 and 12 months
Change in urine specific gravity from baseline to 1 week, 6 and 12 months
Change in renal Doppler flowmetry from baseline to 1 week, 6 and 12 months
Primary:
Change in office BP from baseline to 12 months after the intervention
Secondary:
Change in mean/variability of 24-h, daytime, nighttime BP, nighttime dip and morning surge of BP from baseline to 6 and 12 months
Change in echocardiographic Left Ventricular Mass Index from baseline to 6 and 12 months
Change in intima media thickness of carotid artery from baseline to 6 and 12 months
Change in cardio-ankle vascular index(CAVI) from baseline to 6 and 12 months
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6. How We Do Renal Denervation
Preparation and premedication as usual for renal intervention(ballooning/stenting)
Standard abdominal aortography
6F guiding sheath (IMA, RDC, MP) is advanced over guidewire into the ostium of renal artery
5F ablation catheter(4 mm tip electrode with thermocouple) is advanced through the guiding sheath into the distal part of renal artery
The RF generator is set to temperature control mode with
target t=50 C,
RF power limit=8 watt,
RF timer limit(max duration)=2 min
4-8 point ablations in each artery are performed consecutively from distal part to aorta with 3-4 mm step on the upper, lower, front and back aspects of the artery to get circumferential coverage
Control renal angiography to assess acute safety
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7. How We Do Renal Denervation
Preparation and premedication as usual for renal intervention(ballooning/stenting)
Standard abdominal angiography
6F guiding sheath (IMA, RDC, MP) is advanced over guidewire into the ostium of renal artery
5F ablation catheter(4 mm tip electrode with thermocouple) is advanced through the guiding sheath into the distal part of renal artery
The RF generator is set to temperature control mode with
target t=50 C,
RF power limit=8 watt,
RF timer limit(max duration)=2 min
4-8 point ablations in each artery are performed consecutively from distal part to aorta with 3-4 mm step on the upper, lower, front and back aspects of the artery to get circumferential coverage
Control renal angiography to assess acute safety
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8. Interim Results (Latest Data - April 2012)
Patients
Safety
Number of treated pts 40
Age, years
53.8±9.3
Gender, male
18(45%)
CAD
8(20%)
Diabetes
3(8%)
eGFR, mL/min/1.73m2
82.0(±17.4)
Office BP, mmHg
182.4/106.2
(±22.2/18.6)
24-h mean BP, mmHg
158.4/93.8
(±15.6/13.7)
Number of drugs
4.1±1.2
Use of diuretics
90%
No immediate damage of renal arteries from RF ablation in all 40 cases by intraoperational cineangiography.
5 serious adverse events related to the procedure
Definitely
1 small subcapsular kidney hematoma due to perforation by hydrophilic guidewire (volume estimated by MRI is 80 m L) treated conservatively
1 contrast nephropathy(asymptomatic transient increase in serum Cr)
2 access site hematomas (false aneurysms) not requiring surgery
Probably
1 allergy(skin rash, hypotension, dyspnea) supposedly to contrast media
No significant changes in renal blood flow or renal function at 1st week, 6 months(n=30) and 12 months(n=15) of follow-up.
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9. Interim Results (Latest Data - April 2012)
12 months follow up
Response rate:
office BP – 80%, ABP – 71%
6 months follow up
Response rate:
office BP – 90%, ABP – 55% ** ** ** ** ** ** ** ** ** ** ** ** ** **
** p<0.05, *p<0.01 ** **
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10. Interpretation
Office and ambulatory BP lowering after RD have different time-course:
while most of the office BP decrease develops during first months with only slightly further lowering during the rest of the year
ambulatory BP lowering after RD is a slow linear decline during a year or more with relatively minor effect at 6 months but finally powerful decrease at 12 months (possibly reflecting long- term structural adaptation of CV system to created defect in renal sympathetic regulation)
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11. 20% Of Patients Did Not Respond To RD
Hypothesis:
Methods
BP lowering effect of RD depends on a number of ablations and non-response to RD may be explained by “too low dose” of the treatment
Non-responders to RD with recommended 4-6 ablations per renal artery may respond to repeated procedure with more ablation points
We compared the changes in office and ambulatory BP at 6 months after RD between those with 4-5 ablations per artery(group 1) and those with 6-8 ablations per artery(group 2) We repeated RD in ”higher dose”(more ablation points) in those who remained non-responder (decrease of sBP < 10 mmHg) at 12 months after the primary intervention
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12. Baseline Characteristics of Group 1 (4-5 points per artery) vs Group 2 (6-8 points per artery)
Number of pts with 4-5 ablations per artery completed 6 mo of FU 14
Age, years
49.8±10.3
Gender, male
8(57%)
Office BP, mmHg
190.8/113.9
(±18.2/14.5)
24-h mean BP, mmHg
164.2/100.8
(±17.7/12.8)
Number of drugs
4.3±1.5
Number of pts with 6-8 ablations per artery completed 6 mo of FU 14
Age, years
54.5±8.9
Gender, male
9(64%)
Office BP, mmHg
181.0/99.7*
(±21.9/18.6)
24-h mean BP, mmHg
155.7/90.8
(±14.2/14.4)
Number of drugs
3.6±1.1
The patients in group 2(with more extensive ablation) were a bit older and had slightly lower BP at baseline – potential confounding factor
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13. 6 Months Outcomes In Patients With Different Number Of Ablations Per Artery
6 months after RD with 4-5 points per artery
6 months after RD with 6-8 points per artery
Ambulatory BP lowering after RD was as twice as much in he second group with more extensive ablation(6-8 ablations per artery)
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14. Repeated Renal Denervation In Non-responders
Non-responders At 12 mo After RD
Safety of the repeated procedure
Number of pts
with repeated RD 3
Age, years
45.0±7.5
Gender
1 man/2 women
Office BP, mmHg
184.0/104.7
(±27.7/7.6)
24-h mean BP, mmHg
154.6/95.8
(±11.0/10.4)
eGFR
98.6±34.3
No of ablations per artery in primary RD
4-5
No of ablations per artery in repeated RD
7-8
No immediate damage of renal arteries from RF ablation by intraoperational cineangiography.
The repeated RF procedure was completely uneventful in all 3 cases.
No significant changes in renal blood flow or renal function at 1 week and 6 months of follow-up.
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15. Repeated More Extensive RD In Non-responders: BP Effect
Office BP
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16. Repeated More Extensive RD In Non-responders: BP Effect
Ambulatory BP
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17. Conclusions
Transcatheter RD is safe in patients with resistant hypertension. No damage of renal arteries from RF energy. No sustained damage of renal blood flow or renal function
Transcatheter RD in patients with resistant hypertension is associated with significant decrease of both office and ambulatory BP
Efficacy of RD seems to depend on a number of performed ablations
Repeated RD with more ablation points may be effective in non- responders
7-8 ablations per artery is recommended “dose” of RD to avoid non-responding
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