Catheterization and Cardiovascular Interventions 00:00–00 (2016)

Original Studies

Preliminary Effects of Renal Denervation With Saline

Irrigated Catheter on Cardiac Systolic Function in
Patients With Heart Failure: A Prospective, Randomized,
Controlled, Pilot Study
Weijie Chen,1 Zhiyu Ling,1 Yanping Xu,1 Zengzhang Liu,1 Li Su,1 Huaan Du,1
Peilin Xiao,1 Xianbin Lan,1 Qijun Shan,2 and Yuehui Yin1*

Objective: To assess efficacy and safety of renal denervation (RDN) for heart failure
(HF). Background: RDN has been demonstrated to be an effective method in lowing
overactive sympathetic nerve. However, it’s feasibility and efficacy for HF is unclear.
Methods: In this randomized, controlled pilot study, patients with HF were randomly
assigned in 1:1 ratio to undergo RDN plus optimal medical therapy (RDN group) or only
optimal medical therapy (control group). Before randomization, patients received opti-
mal medical therapy at least half a year. Primary efficacy end point was the change in
LVEF over six months; secondary efficacy end points were the change in six-minute
walk distance and SF-36 Health Survey scores over six months. Results: Up to Apr
2015, sixty symptomatic HF patients were successfully enrolled into study. Thirty
patients were randomly assigned to RDN group and 30 patients were randomly
assigned to control group. All patients completed six months follow up. During follow
up, no severe adverse events were observed. Blood pressure was stable in both
groups. Patients in RDN group had shown a significant improvement in LVEF
(P < 0.001), SMWD (P 5 0.043), NYHA class (P < 0.001), NT-proBNP (P < 0.001) and office
heart rate (P 5 0.008). Compared with control group, RDN patients were associated
with significant improvement in all domains of SF-36 but bodily pain (P 5 0.74). No sig-
nificant change in estimate glomerular filtration nor complication of renal artery steno-
sis were observed. Conclusions: Results imply that RDN could be safely applied to
treatment of HF and probably improve cardiac systolic function and patients’ quality of
life. VC 2016 Wiley Periodicals, Inc.

Key words: heart failure; renal denervation

INTRODUCTION
Heart failure is a public health problem around the
world [1,2]. Treatment of heart failure with renin-
angiotensin-aldosterone system antagonists, beta-
blockers and devices, has made remarkable progress in
recent decades. However, the mortality still remains
very high and approximately 50% of patients diag-
nosed with heart failure will die in 5 years [2].
In heart failure, sympathetic activation is chronically
activated and is involved in maintenance of the patho-
logical state and contribution to continuous progression
in a vicious cycle in the long term [3]. Circulating nor-
1
Department of Cardiology, the Second Affiliated Hospital of
Chongqing Medical University, Chongqing, China
2
Department of Cardiology, the First Affiliated Hospital of
Nanjing Medical University, Nanjing, China
Drs Chen and Ling contributed equally to this paper, and should be
considered as co-first authors.
*Correspondence to: Yuehui Yin, MD. Department of Cardiology,
The Second Affiliated Hospital of Chongqing Medical University,
Chongqing, 400010, China. E-mail:yinyh63@163.com
Received 31 August 2015; Revision accepted 29 January 2016
DOI: 10.1002/ccd.26475
Published online 00 Month 2016 in Wiley Online Library
(wileyonlinelibrary.com)

C 2016 Wiley Periodicals, Inc.

V
2 Chen et al
epinephrine concentrations, as the direct evidence of
global sympathetic tone, are predictive of cardiovascu-
lar outcomes in heart failure [4,5]. Cardiac norepineph-
rine spillovers, as the direct evidence of cardiac
sympathetic tone, are also significantly increased and
closely related to the severity of heart failure [6].
Therefore, the relationship between sympathetic activa-
tion and progression of heart failure raises the possibil-
ity that any medical therapy or intervention targeting
the sympathetic nervous system thereby reducing detri-
mental sympathetic activation may favorably influence
the outcome of patients with heart failure. Beta-
blockers, as the pharmacotherapeutic method to inhibit
sympathetic nerve activity, have been demonstrated to
improve symptoms and decrease mortality of heart fail-
ure [7]. In recent years, catheter-based renal denerva-
tion (RDN) has been safely applied to treat resistant
hypertension and significantly lower blood pressure
[8–11]. Although the SYMPLICITY HTN-3 trial [12]
failed to meet its primary efficacy endpoint, It has
been demonstrated that RDN technique could not only
decrease the renal sympathetic tone but also reduce the
global sympathetic activity [8,13]. However, as an
interventional method to decrease sympathetic nerve
activity, whether RDN technique could be safely
applied for the treatment of heart failure to improve
cardiac systolic function or cardiac remolding process
has not been intensively evaluated.
To investigate the feasibility of RDN applied to
treatment of heart failure, we conducted this random-
ized, controlled, small-scale pilot study and then the
full-scale SWAN-HF study (SouthWestern China renal
Artery sympathetic Nerve ablation study in Heart Fail-
ure; clinicaltrials.gov, identifier: NCT01402726). Here,
we present the preliminary results from the small-scale
pilot study.
METHODS
Study Design and Population
This pilot study was an on-going open-label, pro-
spective, randomized, controlled clinical trial. The
study protocol complied with the Declaration of Hel-
sinki and was approved by the ethics committee of our
research center. Written informed consent was obtained
from each participant before enrollment.
Patients with heart failure maintained on optimal
medical therapy for at least half a year were invited to
participate this pilot study. The inclusion and exclusion
criteria for study participation are summarized in Table
I [14]. There were total of 60 eligible patients,
aged  18 and  75 years. All the enrolled patients suf-
fered from symptomatic heart failure more than half a
year, New York Heart Association (NYHA) Class II to
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
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TABLE I. The Inclusion and Exclusion Criteria
Inclusion criteria
 Symptomatic heart failure patients maintained on optimal medical
therapy for at least half a year
 18  age  75 years old
 NYHA CIass ll to lV
 LVEF  40% measured with Simpson’s method
Exclusion criteria
Presence of:
 Atrial fibrillation
 Congenital or severe valvular heart diseases
 Acute heart failure
 Acute coronary syndrome
 Cardiogenic shock
 SBP <90 mm Hg
 Sick sinus syndrome
 Marked sinus bradycardia (<50 beats/min)
 Sustained ventricular tachyarrhythmia
 Pacemaker or defibrillator use
 Cerebrovascular accidents or alimentary tract hemorrhage within
three months
 History of renal artery stenosis or renal artery stents implantation
 EGFR <45mL/min (according to the modified MDRD equation for
Chinese patients)
 Pregnant women
 Mental disorders
 Allergy to contrast agent
 Severe renal artery anatomy disorders (such as severe distortion or
stenosis, diameter of renal artery < 4 mm and/or length of renal
artery < 2 cm)
 Other clinical conditions that limited the enrollment
NYHA ¼ New York Heart Association; LVEF ¼ left ventricular ejection
fraction; SBP ¼ systolic blood pressure; EGFR ¼ estimated glomerular
filtration rate; HF ¼ heart failure.
EGFR(mL/min/1.73m2) ¼ 186*[serum creatinine (mg/dl)1.154]*(age 
0.203
)*1.233*F(Where F ¼ 1 if male, and 0.742 if female).
IV and echocardiographic left ventricular ejection frac-
tion (LVEF)  40% measured with Simpson’s method.
Study Protocol
All symptomatic patients were randomly assigned in
a 1 : 1 ratio to RDN group or control group. Patients
in control group received optimal medical treatment
during follow-up period, including beta-blockers,
ACEIs/ARBs, aldosterone antagonists and diuretics in-
dependently of group allocation. Patients in RDN
group received optimal medical treatment plus RDN
therapy and were additionally asked to take aspirin,
clopidogrel and atorvastatin for three months after
ablation procedure to lower the potiential risk of renal
artery thrombosis.
Enrolled patients were followed up every three
months. The baseline characteristics, including medical
history, physical exams, office blood pressure, medica-
tions, renal function, transthoracic echocardiography,
6-min walk test, NYHA classification and the MOS

36-Item Short Form Health Survey (SF-36) were per-
formed and recorded. The patients who were excluded
due to renal artery disorders were also followed up at
1 and 3 months.
Echocardiography examination was performed using
iE33 ultrasound systems (Philips, Netherlands) at base-
line, 3 months and 6 months according to the guide-
lines constituted by American Society of
echocardiography [15], and the results were analyzed
by two independently ultrasonic experts blinded to the
patients’ group.
Six-minute walk test was performed in an indoor
corridor in length of 30 m according to the guidelines
of American Thoracic Society at baseline, 3 months
and 6 months [16–18]. All patients were instructed and
tested by two independently attending physicians
blinded to patients’ group and follow-up status.
The SF-36 health survey used in this pilot study was
a Chinese version. It consisted of a short 36-item ques-
tionnaire which measured eight domains: physical
functioning (10 items;), role limitations due to physical
problems (four items), role limitations due to emotional
problems (three items), bodily pain (two items), vitality
(four items), mental health (five items), social function-
ing (two items) and general health (five items). This
Chinese SF-36 Health survey was a translation from
original English version [19,20]. Higher scores of each
domain signified better health status according to the
SF-36 instruction.
Interventional Procedure
RDN procedure was performed with the use of sa-
line irrigated catheter (ThermocoolV R catheter, Celcius
Thermocool, Biosense Webster, Diamond Bar, CA).
Under local anesthesia, right femoral artery puncture
was performed. 2000-3000 IU heparin was given via
right femoral artery. Conventional bilateral renal artery
angiography was performed with the use of JR4 Jud-
kins catheter (Cordis corporation Miami, FL). If the
anatomic structure of renal arteries was appropriate for
RDN, bilateral RDN was conducted. Prior to RDN,
one-tenth milligram of fentanyl was intravenously
injected to alleviate waist pain caused by radiofre-
quency energy delivery. RDN procedure was per-
formed from distal to proximal by point to point.
Number of lesion points for each renal artery depended
on its length. Radiofrequency energy was approxi-
mately 8  12 Watts persisted 60  80 sec for each
lesion point. Saline was manually irrigated during abla-
tion procedure to decrease the interface temperature
between tissue and catheter, while the speed of saline
was altered according to temperature of catheter tip.
The cutoff temperature of catheter was 45 deg C. Bilat-
Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Preliminary Effects of Renal Denervation 3
eral renal artery angiography was repeatedly performed
after ablation to review the safety of renal artery. Ni-
troglycerin was directly injected to renal artery via a
Judkins catheter when significant spasm was observed,
and stent would be implanted to cure severe stenosis if
indicated.
End Points of the Study
Primary end point was the change in LVEF within
six months after randomization. In addition, safety of
RDN with saline irrigated catheter, 6-min walk test
and SF-36 Health Survey were also evaluated.
Statistical Analysis
Continuous variables were presented with mean-
 standard deviation. Dichotomous variables were
reported as numbers (percentages). The comparability
of baseline characteristics between the two groups was
assessed with the use of two-sample Student’s t-test for
continuous variables and the chi-square test or Wil-
coxon test, when appropriate, for categorical variables.
Comparison of the differences between groups over 6
months was performed with the use of a two-way
repeated measures ANOVA in general linear model.
The two groups as a between-subjects factor (group)
and the repeated measurements during 6 months as the
within-subjects factor (time) were considered. If the
two-way repeated measures ANOVA was significant,
post hoc analysis with the use of Fisher’s Least Signifi-
cant Difference (LSD) Test was performed. A two-
sided alpha level of 0.05 was used for all superiority
tests. All statistical analysis were performed with SPSS
statistics software (version 17.00, Chicago, IL).
Sample Size Estimation
In this pilot study protocol, the increase of LVEF in
RDN group was primarily estimated 10% higher than
that in control group with 10% standard deviation dur-
ing 6 months follow up. Therefore, sample size estima-
tion was conducted by using two-sample Student’s t-
test, accepting a two-sided alpha level of 0.05 with
power of 0.9. The necessary sample size in RDN group
was 21. With the assigned rate of 1:1 in control group,
at least 42 heart failure patients should been enrolled
into the this pilot study.
RESULTS
Patient Characteristics
From July 2011 to Oct 2014, of the 64 patients
screened for enrollment, 60 eligible patients were suc-
cessfully enrolled into this study while the other four
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
4 Chen et al

TABLE II. Baseline Demographic and Clinical Characteristics

Variables RDN group (n ¼ 30) Control group (n ¼ 30) P
Male (sex) 22(73.3%) 24(80%) 0.23
Age (years) 48.5  8.4 50.5  7.7 0.94
BMI (kg/m2) 24.2  2.8 23.6  2.4 0.53
History Of HF(months) 21.6  6.5 23.8  7.1 0.60
NYHA class 3.2  0.5 3.1  0.4 0.55
Comorbidity
Hypertension 8(26.7%) 7(23.3%)
Cardiomyopathy 16(53.3%) 18(60%)
Ischemic cardiomyopathy 6(20%) 5(16.7%)
Medical Therapy History
ACEI/ARB 30(100%) 30(100%)
Beta-blockers 28(93.3%) 29(96.7%)
Aldosterone antagonists 28(93.3%) 27(90%)
Furosemide 21(70%) 24(80%)
Digoxin 7(23.3%) 9(30%)
Office Heart Rate (beats/minutes) 78.6  10.6 79.7  12.6 0.72
Baseline SBP (mm Hg) 110.6  16.5 108.6  12.8 0.59
Baseline DBP (mm Hg) 70.5  11.1 68.9  9.1 0.54
eGFR(ml/min/1.73 m2) 94.4  17.9 97.7  18.0 0.56
NT-ProBNP (pg/ml) 1519.9  599.3 1595.0  707.7 0.66
Continuous variables are mean  standard deviation; Dichotomous variables are reported as numbers (percentages). ACEI ¼ angiotensin-converting-
enzyme inhibitors; ARB ¼ Angiotensin receptor blockers; BMI ¼ body mass index; DBP ¼ diastolic blood pressure; eGFR ¼ estimated glomerular fil-
tration rate. HF ¼ heart failure; SBP ¼ systolic blood pressure; eGFR(ml/min/1.73 m2)¼186*[serum creatinine (mg/dl)1.154]*(age0.203)*1.233*F(-
Where F ¼1 if male, and 0.742 if female). See text for further description.

patients were excluded because of the inappropriate re-
nal artery anatomy problems. Of these 60 enrolled
patients, thirty patients were randomly assigned to
RDN group and the other 30 patients were randomly
assigned to Control group. Up to Apr 2015, these 60
enrolled patients in two groups had completed 6
months follow up, and the results are reported in this
paper. The baseline demographic and clinical charac-
teristics of enrolled patients are shown in Table II.
There was no imbalance in demographic characteristics
including age, sex, or BMI. The medical therapy his-
tory and comorbidity were similar between groups at
baseline. Additionally, no significant differences were
found in heart failure history, NYHA class, and NT-
ProBNP level between RDN group and control group
at baseline.
Pharmacotherapy
All patients in both groups were maintained on opti-
mal medical therapies pre- and post-enrollment. There
were no significant differences in dose of ACEI/ARB,
beta-blockers and aldosterone antagonists between two
groups over six months follow-up periods. However,
the use of furosemide in RDN group was significantly
decreased compared with that in control group during
six months follow up(46.7% at baseline to 23.3% at 6
months in RDN group vs. 60% at baseline to 66.7% at
6 months in control group. P < 0.001).
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Ablation Procedure Characteristics
In RDN group, the renal artery ablation procedure
(Fig. 1C) was bilaterally performed with 6.7  0.8 and
7.0  1.0 lesions for left and right renal artery, respec-
tively (Table III). The average radiofrequency time for
each lesion was 68.8  3.6 sec, while the total radiofre-
quency delivery time was 942.1  103.3 sec for each
patient. Actual power was 10.2  1.2 watts, and the
temperature was 40.1  0.8 deg C during ablation pro-
cedure. Impedance was 161.8  17.9 ohms, and the
total procedural time was 75.4  7.4 min on average.
Primary Endpoints
The LVEF was progressively increased in RDN group
(Fig. 2A), from 31.1  5.7% at baseline to 39.3  7.8%
at 3 months and to 41.9  7.9% at 6 months, whereas
LVEF showed no increase or even slightly decrease in
control group, from 31.9  6.0% at baseline to
31.4  5.7% at 3 months and to 31.2  5.5% at 6
months. The LVEF in RDN group were significantly
improved compared with that in control group over 6
months follow up (P < 0.001) (Fig. 2A).
Other Outcome Parameters
Six-minute walk test. The SMWD in RDN group
was significantly improved compared with that in control
group over 6 months follow up (from 285.5  84.3 m at
baseline to 324.2  84.8 m at 3 months to 374.9  91.9 m
 Preliminary Effects of Renal Denervation 5

Fig. 1. Angiography and ablation procedure of right renal ar-
tery. Angiography of right renal artery preablation (A); during
radiofrequency ablation procedure (B); immediately following
renal sympathetic denervation (C); Angiography of right renal
artery at 6 months of follow-up (D); ablation trace ("); Ablation
trace of renal artery endothelium was observed immediately
following ablation procedure, however, the ablation trace was
disappeared at 6 months follow-up. See text for further
description. [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]

TABLE III. Renal Denervation Procedural Variables SF-36 health survey and other heart failure
markers. Quality of life evaluated by SF-36 in RDN
Procedure Variables Mean  SD
group was significantly improved compared with that
Lesion NO. Left Renal Artery 6.7  0.8 in control group over 6 months follow up (P ¼ 0.74 for
Right Renal Arter 7.0  1.0
Average lesion duration(S) 68.8  3.6
bodily pain, P  0.001 for other domains) (Fig. 3). The
Total radiofrequency(S) 942.1  103.3 NYHA classification in RDN groups was obviously
Average power(W) 10.2  1.2 decreased from 3.2  0.5 to 1.6  0.6 over six months
Average temperature (8C) 40.1  0.8 follow up compared with that in control group
Average impedance(X) 161.8  17.9 (P < 0.001) (Fig. 2C). Office heart rate in RDN group
Procedure duration(Min) 75.4  7.4
was significantly decreased compared with that in con-
See text for further description. trol group over 6 months follow up (from 78.6  10.6
beats/min at baseline to 74.2  8.9 beats/min at three
at six months in RDN group. However, it has no signifi- months to 69.2  7.2 beats/min at six months in RDN
cant change from baseline to 6 months follow up in con- group; from 79.7  12.6 beats/min at baseline to
trol group. P ¼ 0.043) (Fig. 2B). 80.0  10.2 beats/min at three months to 81.4  6.4
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
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6 Chen et al

Fig. 2. Comparison of main outcomes between RDN group and control group. Note. ***
equal P < 0.001; NS 5 nonsignificant difference; SMWD 5 6-min walk distance; See text for fur-
ther description.

beats/min at six months in control group. P ¼ 0.008)
(Table IV). In addition, N-terminal pro–B-type natri-
uretic peptide (NT-proBNP), as an indicator of heart
failure, was significantly decreased in RDN group
compared with that in control group over 6 months fol-
low up (P < 0.001) (Fig. 2D).
Other echocardiographic parameters. As shown
in Table IV, interventricular septal motion amplitude
(IVSMA) and left ventricular posterior wall motion
amplitude (LVPWMA), as predictors of cardiac sys-
tolic function in RDN group were significantly
improved compared with those of control group over 6
months (P < 0.05 for both variables). The other heart
chamber diameter, including the left atrium diameter
(LAD), right atrium diameter (RAD), left ventricular
end-diastolic diameter (LVEDD), and right ventricular
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
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end-diastolic diameter (RVEDD) between two groups
showed no significant differences over 6 months, while
these variables in RDN group had obvious trend of
improvement compared with that in control group (Ta-
ble IV).
Safety
There were no severe adverse events during ablation
procedure and follow-up periods. The systolic/diastolic
blood pressure (SBP/DBP) in RDN group did not show
any statistical difference compared with those in the
control group at baseline or follow-up periods (Table
IV). EGFR did not change during follow up as shown
in Table IV. However, slight injury of renal artery en-
dothelium was observed immediately post-ablation
comparing with pre-ablation in five patients, but no
 Preliminary Effects of Renal Denervation 7

Fig. 3. Results of the MOS 36-item Short Form Health Survey (SF-36). Note. *** equal
P < 0.001; NS 5 nonsignificant difference; See text for further description.

TABLE IV. The Results of Cardiac Chamber Dimensions, Blood Pressure, Heart Rate, and eGFR in Two Groups
P value for RDN
goup vs. control
group over
RDN group (n ¼ 30) Control group (n ¼ 30)
Parameters 6 months
Baseline 3 Months 6 Months Baseline 3 Months 6 Months
LAD (mm) 46.1  5.1 42.5  5.5 39.3  5.7 45.1  4.8 44.0  3.6 44.3  4.3 0.111
RAD (mm) 39.9  5.6 37.4  5.5 37.0  4.4 40.1  4.2 40.1  4.3 40.5  4.1 0.060
LVEDD (mm) 65.3  5.2 61.8  7.2 59.4  7.0 64.2  4.8 63.9  5.0 64.5  4.2 0.143
RVEDD (mm) 24.9  3.1 23.4  3.4 22.7  3.0 24.6  2.7 24.5  3.4 24.6  3.6 0.218
IVSMA (mm) 6.2  2.0 7.8  1.9 8.9  1.9 6.8  2.1 6.7  2.0 6.4  1.8 0.028
LVPWMA (mm) 7.1  1.9 8.8  1.5 9.2  1.9 6.9  2.1 7.3  1.8 6.7  1.6 0.001
FS (%) 18.9  5.0 25.7  5.4 28.8  7.1 21.7  6.1 21.9  5.9 21.0  5.0 0.019
SBP (mm Hg) 110.6  16.5 108.8  11.3 106.2  11.4 108.6  12.8 106.5  13.5 105.5  13.8 0.613
DBP (mm Hg) 70.5  11.1 70.1  9.6 68.2  7.8 68.9  9.1 68.1  8.7 66.1  6.6 0.388
Office heart rate 78.6  10.6 74.2  8.9 69.2  7.2 79.7  12.6 80.0  10.2 81.4  6.4 0.008
(beats/min)
NT-proBNP (pg/ml) 1519.9  599.3 798.9  346.3 422.7  257.0 1595.0  707.7 1497.4  708.7 ’1447.8  674.9 <0.001
eGFR (ml/min/1.73m2) 94.4  18.0 102.4  21.6 108.3  21.7 97.1  18.0 100.2  21.6 99.8  21.8 0.602
Values are mean  SD. LAD ¼ left atrium diameter; RAD ¼ right atrium diameter; LVEDD ¼ left ventricular end-diastolic diameter; RVEDD ¼ right
ventricular end-diastolic diameter; IVSMA ¼ interventricular septal motion amplitude; LVPWMA ¼ left ventricular posterior wall motion amplitude;
FS ¼ fractional shortening; SBP ¼ systolic blood pressure; DBP ¼ diastolic blood pressure; NT-proBNP ¼ N-terminal pro–B-type natriuretic peptide.
eGFR(mL/min/1.73m2)¼186*[serum creatinine (mg/dl)1.154]*(age 0.203)*1.233*F(Where F ¼1 if male, and 0.742 if female). See text for further
description.

acute stenosis or dissection was found (Fig. 1C). Dur-

ing 6 months follow up, six patients underwent renal
artery angiography, no stenosis was observed, and the
initial injury of renal artery endothelium had com-
pletely healed (Fig. 1D). All patients experienced waist
pain during radiofrequency energy delivery, but it dis-
appeared immediately after interruption of radiofre-
quency energy delivery, and 12/30 (40%) need
additional intramuscularly analgesics during radiofre-
quency energy delivery.
Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
DISCUSSION
The question addressed by this pilot study was the
feasibility of catheter-based RDN technique applied to
the treatment of heart failure. We found that catheter-
based RDN technique could be safely applied to the
treatment of heart failure and probably improve cardiac
systolic function and even the patients’ quality of life.
The preliminary result showed that LVEF in RDN
group increased by 10% over 6 months follow-up
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.
8 Chen et al
period (from 31.1  5.7% at baseline to 41.9  7.9% at
6 months). The other endpoints of cardiac systolic
function, including SMWD, NYHA class, IVSMA and
LVPWMA, were also significantly improved over 6
months follow-up period in RDN group. In addition,
the patients’ quality of life evaluated by SF-36 signifi-
cantly improved in multiple domains except bodily
pain over six months after ablation.
The main findings of this pilot study were consistent
with the previously published data of REACH-Pilot
study [21] regarding catheter-based RDN technique in
treatment of heart failure, which also showed the safely
of RDN in heart failure and the improvements of
symptom and exercise capacity of patients. The other
pilot study Olomouc-1, presented at the Congress of
the European Society of Cardiology in 2012, also com-
pared the safety and effects of RDN plus medical ther-
apy with only optimal medical therapy in 51 patients
with advanced heart failure, and demonstrated that in
addition to increasing LVEF, the RDN group even
decreased the left ventricular dimensions and mean
heart rate.
Up to now, this pilot study, the published REACH-
Pilot study and the presented Olomouc-1 pilot study all
implied that RDN could be safely and effectively
applied to the treatment of heart failure, with the possi-
bility to improve cardiac systolic function and quality
of life. What’s the possible explanations for these clini-
cal findings? The decrease of sympathetic activity con-
ducted by RDN maybe one of the most important
pathophysiological mechanism. Previous study [8,13]
demonstrated that mean renal noradrenaline spillover
was decreased by 47% and the whole-body norepi-
nephrine spillover was reduced by 42% via using RDN
technique. Ukena et al. [22] also demonstrated that
heart rate as an indicator of sympathetic tone was also
decreased by RDN. These studies suggested that renal,
cardiac, or even the whole-body sympathetic activity
were decreased by catheter-based RDN. It has been
demonstrated that indicator of global or local sympa-
thetic activity, including circulating norepinephrine
concentrations, renal noradrenaline spillover and car-
diac sympathetic tone, has important prognostic value
in heart failure patients. And decreasing the global or
local (including renal and cardiac) sympathetic acitivity
predicts improvements of cardiovasucular outcomes
and survival. Therefore, the effects on decreasing cir-
culating, renal and cardiac sympathetic activity of
RDN maybe contribute to the improvement of cardiac
systolic function and patients’ quality of life.
It is known that SYMPLICITY HTN-3 trial [12]
failed to meet its primary efficacy endpoint. After in-
depth analysis of SYMPLICITY HTN-3 data, some
limitations refered to the design and performance of
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Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
HTN-3 have been proposed [23–25]. Insufficient dener-
vation conducted by temperature-controlled radiofre-
quency catheter, is one of the limitations in focus.
However, in this pilot study, saline irrigated catheter
was used to perform RDN. As previous studies shown,
compared with temperature-controlled catheter, saline
irrigated catheter may produce much wider and deeper
destruction to renal sympathetic nerve with low risk of
coagulum formation [26–28]. Thus, as demonstrated by
this study, saline irrigated catheter can be safely and
effectively applied to RDN therapy of HF.
STUDY LIMITATIONS
As a pilot study, limitations of this article include
small number of sample-size and the relatively short
follow-up period. However, primary focus of this study
was on the feasibility and safety of RDN with saline
irrigated catheter in HF patients. Future results of the
following large-scale SWAN-HF study with longer
follow-up period will be anticipating. More multicen-
ters, double-blind, randomized, controlled clinical trials
on RDN in HF will be necessary to confirm the
results.
CONCLUSIONS
Catheter-based renal denervation using saline irri-
gated catheter could be safely applied to the treatment
of HF and even improve the cardiac systolic function
and patients’ quality of life.
Conflict of interest: Nothing to report.
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Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.