Curr Cardiol Rep

DOI 10.1007/s11886-012-0258-x

CONGESTIVE HEART FAILURE (J LINDENFELD, SECTION EDITOR)

The Role of Renal Denervation in the Treatment

of Heart Failure
Paul A. Sobotka & Henry Krum & Michael Bhm &
Darrel P. Francis & Markus P. Schlaich

# Springer Science+Business Media, LLC 2012

Abstract The heart and kidney interact in terms of hemo-
dynamics and neurohumoral regulatory mechanisms, and
this helps to maintain circulatory homeostasis under normal
conditions. However, the normal regulatory mechanisms
become inappropriate in the setting of congestive heart
failure (CHF), and significant renal dysfunction often devel-
ops in CHF patients. Activation of renal sympathetic effer-
ent nerves causes renin release, sodium and water retention,
and reduced renal blood flow, all hallmarks of the renal
manifestations of CHF. An increase in plasma levels of
P. A. Sobotka
Medtronic, Vascular,
Santa Rosa, CA, USA
H. Krum
Centre of Cardiovascular Research and Education in Therapeutics,
Department of Epidemiology and Preventive Medicine,
Monash University,
Melbourne, VIC, Australia
M. Bhm
Klinik fr Innere Medizin III, Universittsklinikum des Saarlandes,
Homburg/Saar, Germany
D. P. Francis
International Centre for Circulatory Health,
St Marys Hospital and Imperial College,
59-61 North Wharf Road,
W2 1LA, London, UK
M. P. Schlaich
Baker IDI Heart and Diabetes Institute,
Melbourne, VIC, Australia
P. A. Sobotka (*)
2015 Marywood Lane, West Street,
Paul, MN 55118, USA
e-mail: paul.a.sobotka@medtronic.com
angiotensin II that is mediated in part by renal sympathetic
activation has an effect on the central nervous system to
further increase global sympathetic tone. Renal sympathetic
activity can be assessed clinically by renal norepinephrine
spillover, and an increase in renal norepinephrine spillover
in CHF predicts reduced survival. In addition to efferent
sympathetic activation, activation of renal sensory nerves in
CHF may cause a reflex increase in sympathetic tone that
contributes to elevated peripheral vascular resistance and
vascular remodeling as well as left ventricular remodeling
and dysfunction. In animal models of heart failure, surgical
renal denervation has been shown to improve both renal and
ventricular function. Although surgical renal denervation
has long been known to lower blood pressure and improve
survival in patients with hypertension, the invasive nature of
this approach and its associated complications has limited its
appeal. However, a novel catheter-based device has recently
been introduced that specifically interrupts both efferent and
afferent renal nerves, and there is significant interest in the
use of this device to treat both hypertension and CHF.
Several ongoing clinical trials are investigating the safety
and efficacy of renal denervation in patients with CHF.
Keywords Norepinephrine . Sympathetic . Angiotensin .
Kidney . Renal blood flow . Clinical trial . Renal denervation .
Heart failure
Introduction
Renal dysfunction plays a seminal role in the development
and progression of congestive heart failure (CHF). The
majority of patients hospitalized for acute decompensated
CHF have been shown to have some degree of renal dys-
function [1]. The renal nerves are thought to play an

important role in the renal dysfunction that occurs in CHF,
since renal sympathetic efferent activation causes renin
release, sodium and water retention, and reduced renal
blood flow (RBF) [2, 3]. Renal sympathetic activation
has important prognostic value in CHF patients, since
increased renal norepinephrine spillover predicts reduced
survival [4]. In addition to efferent sympathetic activation,
activation of renal sensory nerves in CHF may cause a
reflex increase in sympathetic tone that contributes to the
progression of CHF [5].
Renal denervation has long been known to lower blood
pressure and improve survival in patients with hypertension
[6], but the risks associated with the open surgery required
to denervate the kidneys have limited its appeal. In the last
2 years, a novel catheter-based device has become available
that specifically interrupts both efferent and afferent renal
nerves [7], which might become an avenue of therapy for
both hypertension and CHF. This review summarizes the
current information on the role of efferent and afferent renal
nerves in the pathogenesis and progression of CHF, and
describes ongoing clinical trials that will evaluate the safety
and efficacy of catheter-based renal denervation in well-
defined CHF populations.
Functional Anatomy of the Renal Nerves
The efferent renal sympathetic nerves modulate renal func-
tion through the release of local neurotransmitters. Although
immunofluorescent and immunocytochemical methods have
identified a large number of substances in renal nerve ter-
minals, only neuropeptide Y and norepinephrine are thought
to act as true neurotransmitters [8]. These two substances are
released in response to renal nerve activation and bind to
specific post-junctional receptors in the kidney. Direct stim-
ulation of the renal sympathetic nerves results in frequency-
dependent renal vasoconstriction. Sympathetic activation
causes greater constriction of afferent arterioles to the glo-
merulus than efferent arterioles, causing a drop in glomeru-
lar pressure and glomerular filtration rate (GFR). In
addition, sympathetic activation reduces blood flow to both
the renal cortex and medulla. The renal vasoconstriction
induced by sympathetic efferent stimulation results from
norepinephrine acting predominantly on 1-adrenergic
receptors and neuropeptide Y acting on Y1 receptors [9].
Since changes in renal sympathetic tone may influence
RBF and GFR, which in turn influence sodium and water
excretion, it is difficult to determine whether there is any
direct effect of renal nerve activity on the tubular handling
of salt and water. In animal models of sodium overload,
blockade of renal -adrenergic receptors or renal denerva-
tion increases urinary sodium excretion in the absence of
changes in renal hemodynamic parameters [10]. These
Curr Cardiol Rep
findings suggest that there exists a level of efferent renal
sympathetic nerve activity that can directly affect renal
tubular sodium and water reabsorption independent of
changes in GFR, RBF, or the intrarenal distribution of blood
flow. When the renal sympathetic nerves are directly stim-
ulated at a frequency that is subthreshold for renal vasocon-
striction, there is a reversible decrease in urinary sodium
excretion without a change in renal perfusion pressure,
GFR, RBF, or the intrarenal distribution of blood flow
(Table 1) [10]. This direct antinatriuretic effect of sympa-
thetic activation appears to be mediated by 1-adrenergic
receptors.
In addition to neural influences on blood flow and tubular
secretion of sodium, the renal sympathetic nerves also
stimulate the release of renin from juxtaglomerular cells
(Table 1), which is thought to be meditated by activation
of 1-adrenergic receptors with a subsequent increase in
cAMP [11, 12]. This mechanism of renin release is inde-
pendent from but complementary to the release of renin
mediated by the vascular baroreceptor mechanism in the
afferent arterioles of the juxtaglomerular apparatus and the
tubular macula densa mechanism that responds to the sodi-
um load in the distal tubule [12]. In addition, renal sympa-
thetic tone appears to modulate the expression of renin
mRNA in the kidney [13].
Although efferent sympathetic activity mediates changes
in renal function, the kidney also has an extensive network
of afferent unmyelinated fibers that transmit important sen-
sory information to the central nervous system (CNS) [8,
14]. Afferent fibers from the kidney have been shown to
travel along with the sympathetic nerves at the level of the
kidney and then enter the dorsal roots and project to neurons
at both spinal and supraspinal levels. Most of the brainstem
regions involved in cardiovascular control including the
hypothalamus receive inputs from the renal afferents. Renal
afferents are thought to carry information to the CNS from
renal chemoreceptors that respond to changes in the com-
position of the interstitial fluid environment, and mechanor-
eceptors that monitor hydrostatic pressure changes within
Table 1 Changes in renal function at different frequencies of RNS
Frequency of RNS, Hz Renin Na+ GFR RBF
release excretion
0.25 NC NC NC NC
0.50 NC NC NC
1.00 NC NC
2.00
Up arrow ()0increase; down arrow ()0decrease.
GFR glomerular filtration rate, NC no change, RBF renal blood flow,
RNS renal nerve stimulation.
(Adapted from DiBona and Kopp [8].)
Curr Cardiol Rep

the kidneys. Mechanoreceptors are located both in the renal conscious sheep with pacing-induced heart failure, direct
cortex and in the renal pelvis, whereas chemoreceptive recordings of both renal and cardiac sympathetic nerve
nerve endings are found primarily in the submucosal layers activity showed increased discharge rates of both of these
of the renal pelvis [8, 14]. Direct electrical stimulation of the nerves compared with their discharge rates in control
renal afferent nerves in animals may produce both sympa- animals [19].
thoinhibitory and sympathoexcitatory reflexes, which There are multiple afferent inputs that regulate efferent
reflects the diverse functional nature of various populations renal sympathetic outflow from the CNS in CHF. There is a
of renal receptors [14]. Much less is known about the reduced sensitivity of both aortic and carotid baroreflexes
normal function of the renal afferent nerves than the efferent and this may play a role in increased central sympathetic
nerves, but there is evidence that renal afferents play a role outflow and efferent renal nerve activity [20, 21]. Further-
in the reflex increase in sympathetic tone that occurs in more, low pressure cardiopulmonary stretch receptors
hypertension [15, 16]. Presumably, the renal afferents also with vagal afferents have a reduced ability to modulate
mediate a reflex increase in sympathetic tone in CHF, but sympathetic tone in CHF [20, 21]. Enhanced sensitivity
this has not yet been confirmed in humans or experimental of peripheral and central arterial chemoreceptors may
animals. also contribute to an increase in sympathetic tone [22, 23].
Importantly, peripheral chemoreceptor hypersensitivity has
been shown to influence cardiovascular prognosis in patients
Efferent Renal Nerve Activation in CHF with CHF [23].
In addition to changes in reflex input to the CNS in CHF,
In CHF, the sympathetic nervous system is activated there appears to be a change in the CNS integration and
earlier than the renin-angiotensin-aldosterone system processing of afferent input that causes an increase in sym-
[17]. This increase in global sympathetic activity affects pathetic outflow [21]. It is likely that the direct effects of
all vascular beds, with preferential activation of sympa- angiotensin II on the CNS play an important role in medi-
thetic nerves to the heart and kidney, as demonstrated by ating the increase in sympathetic outflow in CHF [21]. The
a pronounced norepinephrine overflow from these two central effects of angiotensin II may function as part of a
organs to plasma [18]. The spillover of norepinephrine positive feedback cycle, where an increase in central sym-
from the kidney was shown to predict all-cause mortality pathetic outflow increases circulating levels of angiotensin
and the need for cardiac transplantation in CHF patients II that results in a further increase in sympathetic outflow.
[4]. Moreover, the predictive value of renal norepineph- The increase in sympathetic activity may start as a compen-
rine spillover was independent of overall sympathetic satory response to ventricular dysfunction and reduced car-
activity (total body norepinephrine spillover), GFR, and diac output, but may become part of a pathological positive
left ventricular ejection fraction (LVEF) (Table 2) [4]. In feedback cycle with the progression of CHF.
Although there is a global increase in sympathetic tone in
CHF that is due to CNS integration of all afferent input,
Table 2 The independent effect of renal NE spillover on the combined sympathetic outflow does not increase equally to all organs.
outcome of all-cause mortality and heart transplantation in patients Some vascular beds such as the renal vasculature receive
with HF
greater sympathetic activation than others in the presence of
Independent variable RR 95% CI P value CHF [15, 24]. A disproportionate increase in renal sympa-
thetic activity results in increased renal vascular resistance
HF etiology (ischemic vs nonischemic) 0.5 0.21.2 0.1 compared with other systemic vascular beds, and this results
Age 1.0 0.951.04 0.9 in increased plasma renin activity as well as sodium and
Below median GFR 1.7 0.74.2 0.2 water retention [25]. The disproportionate increase in renal
Below median LVEF 1.5 0.64.0 0.4 sympathetic activity may be an important mechanism that
Below median cardiac index 1.8 0.84.1 0.2 reduces GFR and prevents a compensatory natriuresis
Below median renal blood flow 1.4 0.63.6 0.5 during the progression of CHF [26].
Above median renal NE spillover 3.1 1.27.6 0.01
Above median total body NE spillover 1.5 0.73.4 0.3
Interventions that Reduce Renal Sympathetic Activation
Patients with HF (n061) were followed for a mean of 5.53.7 years.
The data were analyzed in a multivariate Cox regression model.
in CHF
CI confidence interval, GFR glomerular filtration rate, HF heart failure,
LVEF left ventricular ejection fraction, NE norepinephrine, RR relative Although bilateral renal denervation has little effect on
risk. kidney function in normal animals, several studies in animal
(Adapted from Petersson et al. [4].) models of heart failure have established the beneficial

effects of renal denervation. In a rat model of heart failure
induced by left anterior descending artery ligation, increased
sodium retention was abolished by surgical renal denerva-
tion [10]. Surgical renal denervation in dogs with an arte-
riovenous fistula and compensated high-output heart failure
improved the postprandial natriuresis in response to a sodi-
um load (125 mEq) [27]. The therapeutic value of renal
denervation was demonstrated in two other rat models of
heart failure induced by coronary ligation [28, 29]. Surgical
renal denervation was performed prior to coronary ligation
and resulted in reduced ventricular filling pressures and
improved ventricular function after ligation compared to
nondenervated control animals. Renal denervation was also
shown to restore the diuresis and natriuresis in response to
exogenously administered atrial natriuretic peptide in rats
with heart failure induced by coronary ligation [30]. In a
rabbit model of pacing-induced heart failure, there was a
decrease in RBF, an increase in renal vascular resistance, an
increase in the expression of angiotensin II type 1 receptors
in renal cortical vessels, and a decrease in the expression of
angiotensin II type 2 receptors [31]. All of these changes
were prevented by renal denervation prior to the induction
of heart failure. Taken together, the results of these animal
studies suggest that renal denervation may be particularly
useful in the treatment of CHF in patients.
Although there is little information on the effects of renal
denervation in CHF patients, there is indirect evidence for
the beneficial effects of interventions that reduce renal sym-
pathetic activation. The observation of a natriuresis in re-
sponse to acute intrarenal -adrenergic blockade in CHF
patients supports a therapeutic role for reducing the effects
of increased renal sympathetic nerve activity on sodium and
water retention [32]. Renin release from the kidneys is
influenced by 1-adrenergic receptors, and the administra-
tion of blockers without intrinsic sympathomimetic activ-
ity has been shown to reduce plasma renin activity in CHF
patients [33]. Furthermore, the beneficial effects of
angiotensin-converting enzyme inhibitors and angiotensin
II receptor blockers in CHF patients may be mediated in
part by reducing or attenuating the deleterious effects of
renal sympathetic activation. Even the efficacy of loop
diuretics may be influenced by renal sympathetic activity.
A recent study showed that total urine volume and sodium
excretion were considerably greater when CHF patients
received the same dose of furosemide while they were in a
recumbent position for 90 min, as opposed to an upright
posture (sitting or walking on a treadmill) [34]. Plasma
norepinephrine and renin were higher with the upright
posture and these results suggest that the reduced response to
furosemide was due to an increase in renal sympathetic tone.
These findings suggest that renal denervation may enhance
the efficacy of exogenous diuretics administered to CHF
patients.
Curr Cardiol Rep
Although human studies of pharmacology and animal
experiments with renal denervation suggest that reducing
renal sympathetic tone would be beneficial in CHF, it must
be remembered that a trial of central sympathetic nervous
suppression with moxonidine to treat systolic CHF
(MOXCON [Sustained Release Moxonidine for Conges-
tive Heart Failure]) was disappointing [35]. Prolonged-
release moxonidine, which acts on central imidazoline
receptors to reduce sympathetic tone, significantly in-
creased mortality compared with placebo. Since moxoni-
dine causes a dose-dependent reduction in plasma
norepinephrine levels [36], it is possible that the dose
of moxonidine used and the forced dose-titration protocol
in the MOXCON trial may have reduced vital organ
perfusion because of too large a fall in global sympathet-
ic activity. Since multiple mechanisms are responsible for
the increase in sympathetic tone in CHF, it seems un-
likely that renal denervation will reduce sympathetic tone
to the same degree as high-dose moxonidine. Based on a
small number of studies in animals with heart failure,
bilateral renal denervation has not been associated with a
detectable increase in mortality [10, 2731].
Afferent Renal Nerve Activation in CHF
In addition to acting as a target organ for efferent sympa-
thetic signals, the afferent nerves in the kidney may also
play a role in CHF. The precise population of afferent nerves
that are activated and the mechanisms responsible for their
activation are unknown. However, it is likely that increased
renal afferent nerve signals travel to the CNS and induce a
reflex increase in renal sympathetic tone (renorenal reflex),
thereby causing renal vasoconstriction, renin secretion, and
sodium and water retention [37]. Moreover, increased renal
afferent nerve signals that travel to the CNS may also cause
a reflex increase in sympathetic tone to other organs that
have a dense sympathetic innervation, such as the heart and
peripheral vasculature [15, 16]. The CNS in this case serves
as the central component of the reflex arc. It is possible that
a pathological positive feedback cycle at the level of the
kidney may exist, whereby an increase in renal efferent
sympathetic tone leads to an increase in renal afferent nerve
activity, which further increases efferent sympathetic out-
flow from the CNS (Fig. 1).
Although several substances (nitric oxide, calcitonin
gene-related peptide, substance P, H+, adenosine) have been
postulated to stimulate chemosensitive renal afferents under
various conditions [8, 14, 16], adenosine is of particular
interest, since it is readily released by renal proximal tubular
cells directly into the tubular fluid during increased meta-
bolic activity [38]. Furthermore, intrarenal adenosine has
been shown to be elevated in patients with CHF [39], and
Curr Cardiol Rep

Fig. 1 The effects of increased

sympathetic tone in CHF on the
kidneys, heart, and peripheral
vasculature. A positive
feedback cycle is proposed
whereby an increase in
sympathetic outflow from the
CNS results in an increase in
afferent renal traffic. This
increased afferent traffic travels
back to the CNS and leads to a
further increase in sympathetic
outflow from the CNS as part of
a reflex arc. This positive
feedback loop is interrupted
by renal denervation.
CHFcongestive heart failure;
CNScentral nervous system;
RAASrenin-angiotensin-
aldosterone system

it may activate renal afferents resulting in a reflex increase
in sympathetic tone. Studies in conscious dogs after
unilateral nephrectomy have shown that the intrarenal
infusion of adenosine elevates blood pressure and plasma
norepinephrine, and these effects could be blocked by
surgical interruption of renal afferents [16].
Although studies of renal afferent activity in animals or
patients with CHF are limited, there is evidence of renal
afferent activation in other types of kidney dysfunction.
In a partial (5/6) nephrectomy rat model of renal failure
and hypertension, bilateral dorsal rhizotomy prevented
blood pressure elevation, indicating that afferent signal-
ing to the CNS contributed to a rise in sympathetic tone
[40, 41]. In a rat model of one-kidney, one-clip Goldblatt
hypertension, bilateral dorsal rhizotomy significantly at-
tenuated the rise in blood pressure; however, unilateral
rhizotomy on the side of the nephrectomy had no effect
[42]. These findings suggest that the effect of dorsal
rhizotomy was specific for the renal afferents. In another
rat model where unilateral kidney injury was induced by
the intrarenal injection of phenol, surgical denervation of
the phenol-treated kidney prevented a rise in blood pres-
sure and an increase in norepinephrine turnover in the
posterior hypothalamus [42]. In humans with end-stage
renal disease, nephrectomy in patients with or without
kidney transplantation had a similar effect [43]. Nephrec-
tomy of the native non-functioning kidney resulted in a
reduction of muscle sympathetic nerve activity and total
body norepinephrine spillover, confirming the role of
renal afferents in mediating a reflex increase in sympa-
thetic tone.
The invasive nature of nephrectomy or dorsal rhizotomy
has recently been superseded by the application of low-
power radiofrequency (RF) energy via an endovascular
catheter in the renal arteries to accomplish renal denerva-
tion. This method of renal denervation has been used in
patients with hypertension resistant to pharmacologic thera-
py [44]. Following endovascular denervation, blood pres-
sure fell significantly, and elevated muscle sympathetic
nerve activity returned to normal levels [45, 46]. These
findings in combination with a reduction in total body
norepinephrine spillover in drug-resistant hypertensive
patients without established renal disease suggest that there
may be increased renal afferent activity prior to ablation that
causes a reflex increase in global sympathetic tone. In addi-
tion, since angiotensin II has a central action to increase
sympathetic tone, a reduction in circulating levels of angio-
tensin II after renal denervation may also contribute to a
reduction in central sympathetic outflow [21].
Evaluation of Renal Denervation in CHF Patients
The dramatic reduction in renal sympathetic tone as well as
sympathetic tone to other organs after catheter-based renal
denervation in patients with drug-resistant hypertension
suggests that this technique will also be useful in patients
with CHF [7, 44, 45, 46]. Catheter-based renal denerva-
tion involves femoral artery catheterization with the catheter
tip placed in the distal renal artery. RF energy is then applied
to the endothelium, the catheter is pulled back 0.5 cm and
rotated circumferentially so that the RF energy is applied at

a different site. This is repeated four to six times in each
renal artery. The procedure has been shown to very safe with
minimal complications. Although patients may experience
transient pain during the application of RF energy, this pain
is well managed by intravenous sedation. There has been no
clinical evidence of either vessel thrombosis or kidney
embolization, or renal artery dissection that is related to
the application of RF energy.
Studies in rats subjected to renal surgical denervation
have shown that functional reinnervation of the renal vas-
culature begins to occur between 14 and 24 days after
denervation, with complete return of neural function by
8 weeks [47]. It is likely that some efferent sympathetic
reinnervation occurs in patients after catheter-based renal
denervation, although the time course of this response is
unknown. Furthermore, it is difficult to clinically evaluate
the amount of reinnervation, since there are no simple
diagnostic tests that can evaluate the functional innervation
of the kidneys. In contrast to efferent nerves, the afferent
nerves may have less capacity to regenerate [48]. Thus, the
removal of renal afferent activity with renal denervation and
the subsequent effects on central sympathetic outflow may
be sustained. This concept is supported by the finding of a
continued reduction in blood pressure at 2 years of follow-
up in a cohort of hypertensive patients [49].
A prospective clinical trial, Symplicity-HF (Renal Dener-
vation in Patients with Chronic Heart Failure and Renal
Impairment Clinical Trial), is currently underway to evalu-
ate the effects of catheter-based renal denervation in patients
with systolic CHF. The trial will enroll 40 patients who meet
the following inclusion criteria: New York Heart Associa-
tion (NYHA) functional class II to III, LVEF less than 40%,
estimated GFR of 30 to 75 mL/min/1.73 m2, and stable heart
failure medications including furosemide, angiotensin-
converting-enzyme inhibitors or angiotensin receptor
blockers, aldosterone antagonists and blockers. The
primary end points of the study are focused on safety
(adverse events) as well as efficacy, as assessed by cardiac
and/or renal physiological responses to the denervation.
Specifically, ventricular function will be measured by
echocardiography at baseline, 6 months, and 1 year;
and renal function evaluated by estimated GFR at baseline,
1, 3, 6 months, and 1 year. The first 10 patients enrolled will
have the following measurements at baseline, 6, and
12 months: intracardiac pressures (right heart catheterization),
cardiac and renal norepinephrine spillover, heart rate
variability and arrhythmias (Holter monitoring), muscle
sympathetic nerve activity, and RBF (MAG3 imaging).
Another trial, REACH (REnal Artery Denervation in
Chronic Heart Failure), is currently underway to compare
catheter-based renal denervation with sham procedure in
patients with systolic CHF. This trial is focusing on symptoms
and ventilatory responses to exercise and chemoreceptor
Curr Cardiol Rep
stimulation. It will enroll a total of 100 patients with NYHA
class II to IV heart failure, LVEF less than 40%, estimated
GFR greater than 35 mL/min, and on maximal tolerated
pharmacological therapy. They will have assessments at
baseline and 6 months of symptom status, slope of ventilation
to carbon dioxide production on exercise (VE/VCO2 slope),
chemoreflex sensitivity, arrhythmia burden, and ambulatory
blood pressure.
Since CHF patients who are candidates for the
Simplicity-HF and REACH clinical trials should already
be on optimal doses of -adrenergic blockers, and
angiotensin-converting enzyme inhibitors or angiotensin II
receptor blockers when they undergo renal denervation, it is
possible that these drugs may attenuate some the beneficial
effects of renal denervation. However, the doses of these
agents used are usually less than the doses needed to elim-
inate all stimulation of receptors and angiotensin II recep-
tors; thus, these patients may still benefit from renal
denervation. Furthermore, since pure 1-adrenergic agents
are contraindicated in CHF patients because they expand
extracellular and plasma volumes [50], renal denervation
should reverse the effects of increased -adrenergic tone
on renal blood flow, tubular excretion of sodium, and sys-
temic vasoconstriction. In addition, renal denervation
should eliminate the release of other transmitters such as
neuropeptide Y that might also contribute to sympathetical-
ly mediated renal vasoconstriction [9].
Conclusions
Studies in animals and humans suggest that activation of both
efferent and afferent renal nerves play a role in the pathogen-
esis and progression of disease states such as hypertension and
CHF. Surgical renal denervation in animal models of heart
failure has been shown to improve both cardiac and renal
function. There are two ongoing clinical trials investigating
the safety and efficacy of renal denervation in patients with
systolic CHF. The results of these clinical trials should provide
important physiological information on the impact of renal
denervation on renal and cardiac function, as well as informa-
tion that can be used to design other more definitive controlled
trials to determine whether there is therapeutic value of renal
denervation in patients with CHF.
Disclosure Conflicts of interest: P.A. Sobotka: is an employee of
Medtronic, Inc.; receives royalties based on Symplicity System sales;
and has stock/stock options in Medtronic, Inc.; H. Krum: has received
grant support from Ardian/Medtronic; M. Bhm: is on the speakers
bureau for Medtronic.; D.P. Francis: has received grant support from
Medtronic; and has received travel/accommodations expenses covered
or reimbursed from Medtronic; M.P. Schlaich: has received grant
support from Ardian/Medtronic; has received a consulting fee or
Curr Cardiol Rep
honorarium from Ardian/Medtronic; has a board membership with
Pharmaceutical; and has received grant support from the National
Health and Medical Research Council.
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