Edelman, Elazer

Highsmith, Debby

Keating, John

Mahfoud, Felix

O'Fallon, Patrick

Spognardi, Anna-Maria

Stanley, James

Tzafriri, Abraham R.

Wong, Gee

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www.jacctctabstracts2014.com SATURDAY, SEPTEMBER 13, 2014, 5:00 PM–7:00 PMHypertension Therapies Including Renal Denervation
Washington Convention Center, Lower Level, Hall A
Saturday, September 13, 2014, 5:00 PM–7:00 PM
Abstract nos: 402-427
TCT-402
Renal Norepinephrine Reduction Following Radiofrequency Renal Denervation
Correlates with Extent of Nerve Ablation: Roles of Ablation Areas, Anatomy,
and Number of Treatments
Abraham R. Tzafriri1, Felix Mahfoud2, John Keating3, Gee Wong3,
Anna-Maria Spognardi3, James Stanley3, Debby Highsmith4, Patrick O’Fallon4,
Elazer Edelman5
1CBSET Inc., Lexington, MA, 2Saarland University Hospital, Homburg/Saar,
Germany, 3CBSET, Inc., Lexington, MA, 4Cordis/Biosense Webster, Inc. a Johnson &
Johnson Company, Irwindale, CA, 5Harvard-MIT Biomedical Engineering Center,
Cambridge, Massachusetts
Background: Renal denervation is a treatment option for resistant hypertension.
Preclinical models that explain the dependence of efﬁcacy on treatment parameters
can help differentiate and optimize device efﬁcacy.
Methods: A total of 150 porcine renal arteries were treated with an irrigated multi-
electrode helical catheter (Biosense Webster, CA). Between 2-5 electrodes were
activated for 30-60 sec with power set points ranging from 6-20 W. Renal norepi-
nephrine (NEPI) was measured 7 days post treatment and correlated with morphologic
and morphometric assessments of treated sections. Measured nerve distributions and
ablation areas informed a computational model for predicting the percentage of
affected nerves (AN).
Results: NEPI levels across the range of treatment parameters exhibited a threshold-
like, dependence on %AN, remaining in the range of control levels (360 ng/g) up to
AN¼35% and dropping by 50% and 75% as AN increased to 52% and 70%,
respectively. For 15W/30sec treatments, both NEPI and nerve effects tracked with
number of activated electrodes (statistically signiﬁcant for 5 vs 2 electrodes).
Threshold (w50%) nerve and NEPI effects were only attained when 4 electrodes
were powered. Average %AN increased with total ablation area as predicted by the
computational model when accounting for the (average) measured non-uniform radial
nerve distribution, but assuming that electrode-induced ablation areas achieved are
mutually independent and predictable. Deviations from model-predicted %AN
correlated variable nerve locations and sizes and/or deviant ablation areas. In partic-
ular, aberrantly low ablation areas were observed when electrode treatments were
directed at neighboring blood vessels.
Conclusions: Variable ablation effects can be explained by the conﬂuence of variable
nerve locations and sizes and variable ablation shapes. The additive biomarker effects
seen with angularly staggered treatments can be leveraged to optimize device design
(e.g. electrode number and spacing) and treatment protocols (e.g. catheter rotation
between two consecutive treatments) in the face of unknown variable micro-anatomy.
TCT-403
Peripheral Endothelial Function and Sympathetic Inﬂuence on Dermal
Microcirculation Correlate with Long-Term Blood Pressure Response in Renal
Denervation Patients
Alexander Jabs1, Meike Fluhr1, Katharina Beck1, Selina Muxel1, Zsoﬁa Bardonicsek1,
Thomas Munzel1, Tommaso Gori1, Ulrich Hink1
1University of Mainz Medical Center, Mainz, Germany
Background: Renal denervation (RDN) has emerged as an interventional treatment
option for treatment-resistant hypertension. Hypertensive patients are often charac-
terized by an increased sympathetic tone as well as impaired endothelial function.
However, there is a paucity of diagnostic tools to identify those hypertensive patients
that will beneﬁt from RDN (responders), and to proof successful RDN application. We
therefore aimed to investigate the effects of RDN on vascular reactivity and sympa-
thetic vascular response, with the ultimate goal to establish potential markers of
therapeutic success.
Methods: In 23 patients (mean age 64 years, 13 men, mean ambulatory blood pres-
sure monitoring (ABPM) 148/83 mmHg;  3 (mean 4.78) antihypertensive drugs in
adequate dosage and combination) that underwent RDN (Medtronic Symplicity
(n¼16), St. Jude Medical EnligHTN (n¼7)), ﬂow-mediated dilation (FMD) and low
ﬂow-mediated constriction (L-FMC) as non-invasive measures of endothelial function
were assessed. Sympathetic component to vasomotor function in dermal microcircu-
lation was determined by laser Doppler ﬂowmetry.
Results: 13/23 (57%) of the patients showed an ABMP reduction  5mmHg at
6 months and hence were considered RDN-responders. Responders had a mean
ABPM reduction of -21/-6 mmHg as compared to baseline (p  0.003). In these
patients, L-FMC was found to be signiﬁcantly reduced (-2.54 to -4.02, p  0.017), andJACC Vol 64/11/Suppl B j September 13–17, 2014 j TCT Abstracts/Hysympathetic inﬂuence on vascular tone was reduced from 54 to 50 % (p  0.037),
while non-responders did not show any signiﬁcant differences.
Conclusions: Non-invasive endothelial and sympathetic functional assessment pa-
rameters correlate with successful blood pressure reduction responses to renal
denervation in patients with treatment-resistant hypertension. Further and larger scale
studies are necessary to analyze the potential predictive utility of these parameters in
the clinical RDN setting, in particular with regard to optimized patient selection for the
procedure.
TCT-404
First Clinical Experience with Neurotropic Agents for Treatment of Sympathetic
Hypertension
Horst Sievert1, Nicholas N. Kipshidze2, Konstantin Kipiani3, Vato Kipiani3,
Tea Mukhuradze3, Michael Wholey4
1CardioVascular Center Frankfurt, Frankfurt, Germany, 2Lenox Hill Hospital, New
York, United States, 3Center for Vascular and Heart Disease, Tbilisi, Georgia, 4Univ
Texas San Antonio, San Antonio, TX
Background: New device-based solutions to treat hypertension are focused on the
overactive sympathetic nervous system as the therapeutic target. Early results from
electrical stimulation of carotid baroreceptors and energy-based (radiofrequency, ul-
trasound) ablation of renal nerves have shown the ability to reduce blood pressure.
Methods: We investigated a simple, catheter-based approach of delivering neuro-
tropic agents near renal nerves, speciﬁcally targeting nerve axons, to interfere with
sympathetic nerve function. A small volume of NW2013 (proprietary formulation
developed by Northwind Medical, San Jose, CA), was injected into renal artery walls
using an endovascular catheter with microneedles.
Results: Seven (7) patients were technically successfully treated through local
administration of NW2013 near renal nerves. There were no serious procedure-related,
device-related or agent-related complications. Injury to the renal artery wall was
minimal with no spasm, dissections or vessel perforations. Mild to moderate pain was
reported during agent injection, which was managed by 5mg of morphine, and was
signiﬁcantly less compared to energy-based therapies. Five (5) patients completed
their 1-month and 3-month follow ups and were included in the analysis. Mean
systolic/diastolic ofﬁce blood pressure (OBP) and 24-hour ambulatory blood pressure
(ABP) at baseline were 181/92 and 164/105 mm of Hg, respectively. At 1 and
3 months after treatment, the average OBP reduction was 33/8 and 45/8 mm of Hg,
respectively; equivalent ABP decrease was 12/13 and 22/16 mm of Hg. These results
are very promising and demonstrate that treatment of sympathetic hypertension pa-
tients using local delivery of neurotropic agents is safe and feasible. In addition, the
therapy offers advantages over energy-based methods in terms of nerve speciﬁcity,
less pain and cost effectiveness.
Conclusions: Local administration of selective neurotropic agents surrounding renal
arteries seems to be a safe and feasible procedure to treat sympathetic hypertension.
Long-term data from randomized clinical studies are needed to further evaluate efﬁ-
cacy and durability of this procedure.
TCT-405
SYMPLICITY HTN-3: Outcomes in the African-American and non-African
American Populations
John Flack1, George L. Bakris2, David Kandzari3, Barry T. Katzen4, Martin Leon5,
Laura Mauri6, William W. O’Neill7, Suzanne Oparil8, Krishna Rocha-Singh9,
Raymond R. Townsend10, Deepak L. Bhatt11
1Wayne State University, Detroit, United States, 2The University of Chicago Medicine,
Chicago, Illinois, 3Piedmont Heart Institute, Atlanta, United States, 4Baptist Cardiac
and Vascular Institute, Miami, FL, 5Cardiovascular Research Foundation, New York,
United States, 6Harvard Clinical Research Institute, Boston, Massachusetts, 7Henry
Ford Hospital, Detroit, United States, 8University of Alabama, Birmingham, AL,
9Prairie Heart Institute, Springﬁeld, USA, 10University of Pennsylvania, Philadelphia,
PA, 11Harvard Medical School, Boston, MA
Background: SYMPLICITY HTN-3 was a randomized, blinded, sham-controlled
trial of renal denervation (RDN) in patients with resistant hypertension that demon-
strated safety but not efﬁcacy of RDN. Results for the prespeciﬁed African-American
(AA) and non-African American (non-AA) subgroups are presented.
Methods: All patients were required to have an ofﬁce systolic blood pressure (SBP)
160 mm Hg and an ambulatory 24-hour SBP 135 mm Hg while taking 3 anti-
hypertensive drugs at maximally-tolerated dose, including a diuretic. Baseline clinical
and procedural characteristics, baseline and 6-month antihypertensive medication use
and changes in ofﬁce and ambulatory blood pressure were compared between groups.
Results: AA patients comprised (26.2%) of the cohort in this trial. AA were
younger, included more females, had a lower incidence of coronary artery disease
and had a greater incidence of asthma, stroke and heart failure than non-AA patients.
Change in ofﬁce and ambulatory BP measurements are shown in the table. Dif-
ferences in Ofﬁce SBP reduction at 6 months were not apparent at earlier time
points. The use of vasodilators (majority hydralazine) was greater in the AA than the
non-AA subgroup (47% vs 34%, p¼0.03 for RDN patients and 56% vs 41%,
p¼0.09 for sham patients). The SBP decrease in the AA sham group on vasodilators
was -21.9 mm Hg and -12.7 mm Hg in the AA cohort not on vasodilators (p¼0.276;
p for interaction ¼0.185).pertension Therapies Including Renal Denervation B119


TCT-402 Renal Norepinephrine Reduction Following Radiofrequency Renal Denervation Correlates with Extent of Nerve Ablation: Roles of Ablation Areas, Anatomy, and Number of Treatments 

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TCT-402 Renal Norepinephrine Reduction Following Radiofrequency Renal Denervation Correlates with Extent of Nerve Ablation: Roles of Ablation Areas, Anatomy, and Number of Treatments

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