Renal denervation: a glimpse of hope?
Renal denervation: a glimpse of hope?
M. Voskuil 0
0 Department of Cardiology, University Medical Center Utrecht , Utrecht , The Netherlands
The development of the treatment modality using renal
denervation with radiofrequency energy endured many ups
and downs . After encouraging results in the initial
studies, a pronounced variability in blood pressure responses
of individual patients was noted in clinical practice. Trying
to unravel this observed variability, several technical
shortcomings, in addition to the issue of selecting the
appropriate patient population, were distinguished. For example,
the induced lesions had a restricted distribution and
limited penetration depth, leaving a large part of the nerves
in the perivascular areas distant from the vascular lumen
unaffected . This may be due to the increased intima
and media thickness in these hypertensive patients.
Furthermore, the initial advice to perform ablations primarily
in the main renal artery, leaving the distal segments and
side branches untreated, may not have been good advice,
in hindsight. Increased interest in the anatomy of
sympathetic renal innervation has led to several novel insights
. For example, there is a high interpatient variability
in the anatomy of these nerves. However, in general, the
density of renal sympathetic nerves is higher and the
location of these nerves more superficial in the distal segments.
Also, in renal arteries with larger diameters and thicker
vessel parenchyma, the innervation is found further from the
lumen and the nerves increase in thickness. These findings
suggest that the ablation lesions might have been
insufficient with respect to location, depth and, most likely, also
in number, in many cases in the initially performed
The concept of performing a redo procedure in patients
who are non-responders to the initial treatment strategy
seems reasonable in the light of the above-mentioned
limitations. In their manuscript in this issue of The Netherlands
Heart Journal, Daemen et al. describe a case series of three
consecutive non-responders who underwent a
repeat-procedure with a second-generation multi-electrode
radiofrequency catheter . The procedure was performed after an
average of 22 months following first treatment. These
patients showed a decrease in office-based and ambulatory
blood pressure of –27/–6 mm Hg and –15/–13 mm Hg,
respectively, after this second treatment. Notably, no
arterial damage was observed after a follow-up of six months.
Therefore, Daemen et al. conclude that a redo procedure
using this second-generation system, and with new insights
in mind, seems safe and might be of additional value in
these difficult-to-treat patients.
Although the idea of performing a redo procedure in this
situation is appealing, the results of this study must be
considered with caution. First, the manuscript describes a
limited experience in only three patients. Second, the catheters
that were used during the index procedure were
second-generation devices, compared to the Symplicity Flex system in
the initial era of renal denervation. Initially, the patients
did not respond to treatment with either a multi-electrode
system (Vessix V2) or a circumferential ablation technique
(Paradise and OneShot system). With regard to some of
these technical aspects, the EnligHTN system appears to be
similar to the systems that were used in the first procedure.
Third, the patients were ablated only in the proximal
segment of the renal arteries, as described by the authors, in
both the first and the second procedure. This is theoretically
one of the disadvantages of the EnligHTN system; it is too
bulky to enter smaller sized distal or side branches.
Remarkably, the patients still responded better to the second
treatment. Could this be because a higher number of
ablations in total after two procedures increases the chance of
targeting enough nerve bundles to show an effect on blood
pressure? Or is this system somehow more potent, i. e.
capable of deeper ablations, than the other systems? The authors
state, with good reason, that they could not exclude that the
redo procedure might have had a similar effect if devices
other than the EnligHTN system would have been used.
To answer this question, a study with a direct head-to-head
comparison of the different devices should be performed.
With the potential shortcomings in mind, also of the
available second-generation devices, it remains of the
utmost importance that a read-out for renal denervation is
developed. A few small studies have evaluated different
techniques for this reason. Some of the results showed that
renal stimulation-induced blood pressure changes were
correlated with changes in ambulatory blood pressure
measurements after renal denervation . Therefore, the authors
stated that this technique might predict the response to renal
denervation and, as a consequence, could serve as a
readout. Also, other techniques, using, for instance, invasively
assessed renal artery haemodynamics, might be of use in
Recently, the long-awaited results of the Dutch
multicentre Sympathy trial were published . Unfortunately,
these results showed that, as with HTN-3, the effects of
renal denervation were not superior to standard care. The
researchers showed that changes over time in medication
adherence were common and affected treatment estimates
considerably. Therefore, the currently running Spyral HTN
OFF-MED/Spyral HTN ON-MED, which includes patients
without medication or with a firm regime of confirmed
medication use, will be pivotal. If this study (and several others
running right now) does not show positive results over the
coming 12 months, a definite loss of belief in this treatment
modality is difficult to avoid.
In conclusion, the paper by Daemen et al. is hopeful, but
as Aristotle already stated long ago: ‘One swallow (or in
this case, three) does not make a summer’ .
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