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RichardR.Heuser· MarkusP.Schlaich·
DagmaraHering· StefanC.BertogEditors
Renal
Denervation
Treatment and Device-Based
Neuromodulation
SecondEdition
123
Renal Denervation
Richard R. Heuser • Markus P. Schlaich
Dagmara Hering • Stefan C. Bertog
Editors
Renal Denervation
Treatment andDevice-Based
Neuromodulation
Second Edition
Editors
Richard R. Heuser
University of Arizona
Phoenix, AZ, USA
Dagmara Hering
Department of Hypertension and Diabetology
Medical University of Gdańsk
Gdańsk, Poland
Markus P. Schlaich
Dobeny Hypertension Centre, Royal Perth
Hospital
University of Western Australia
Perth, WA, Australia
Stefan C. Bertog
CardioVasculäres Centrum Frankfurt
Frankfurt, Germany
ISBN 978-3-031-38933-7 ISBN 978-3-031-38934-4 (eBook)
https://doi.org/10.1007/978-3-031-38934-4
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023,
Springer-Verlag London
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or
part of the material is concerned, specically the rights of translation, reprinting, reuse of illustrations, recitation,
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imply, even in the absence of a specic statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed
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expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been
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This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Paper in this product is recyclable.
2015
To my Granddaughter Anastasia
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We miss you every day
—Richard R. Heuser
To my wife Ute as well as Uta, Siegfried, Silva, Benjamin, and Niklas
—Stefan C.Bertog
Preface
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We were contacted 6years after our publication of the rst edition of renal denervation requesting an update to our original textbook on renal denervation. I would like to thank Springer
publication and in particular Grant Westin for supporting us in this new endeavor. The question
I had right away is “why to write another textbook.” Many of us in healthcare glean most of
our medical information from downloading articles rather than reading textbooks. That being
said, according to Springer our rst edition of “Renal Denervation” generated a lot of interest
and many downloads of our chapters. There were many challenges that we had to go through
with the second edition. One of them was the Covid-19 crisis and the associated work challenges for everyone involved. The slow down with Covid-19 has resulted in limited resources
for anything other than patient care in the throes of this worldwide pandemic. Our thanks to all
of our authors for participating in this worthy endeavor.
When you describe any new treatment, it is always about needs and there certainly is a need
in treating hypertension. Arterial hypertension is the most important contributor to cardiovascular disease with 70% of Americans and Europeans aware of this. The SPRINT trial opened
up our eyes to the fact that many patients are not getting adequate treatment for hypertension
and if renal denervation works clinically, this would be one way to approach this inadequacy
in cardiovascular care worldwide. At the time of our original textbook, over 60 companies
were pursuing renal denervation. With some of the initial randomized controlled trials having
discouraging results, there was a sharp reduction in this entrepreneurial explosive growth.
Recently, however, this has changed with several novel sham-controlled randomized trials
showing promising results, in not just the short term but up to 3-year follow-up. We also know
that a signicant advance has evolved looking at the renin-angiotensin-aldosterone system to
suggest that renal denervation may also interrupt sympathetic mediated neurohormone pathways as part of its mechanism of action to reduce blood pressure. The biggest impetus for us
as clinicians is that patients frequently do not take medication if they have high blood pressure.
Now we have seven trials suggesting that arterial renal denervation produced clinically meaningful and lasting blood pressure reduction, independent of concomitant antihypertensive
medications. With long-term safety and efcacy prole, renal denervation looks to be an
adjunctive treatment modality to medication and lifestyle modication for the management of
patients with hypertension. Our newer edition discusses some other treatments such as targeting the carotid body sinus as well as pacemaker-mediated blood pressure reduction. Also, there
may be some evidence that approaching the nerves in the collecting system of the kidney may
also be an alternative to approaching the nerves paralleling the renal arteries.
Phoenix, AZ, USA RichardR.Heuser
Perth, WA, Australia MarkusP.Schlaich
Gdańsk, Poland DagmaraHering
Frankfurt, Germany StefanC.Bertog
vii
Contents
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Part I Physiology, Anatomy, Pivotal Hypertension Trials and Considerations
for Trial Design
1 Renal Nerves: Roles in Homeostasis and Pathophysiology . . . . . . . . . . . . . . . . . . . 3
Roman Tyshynsky, Lucy Vulchanova, and John Osborn
2 Animal and Human Experience in Quantifying the Effects
of Renal Denervation on Sympathetic Nervous System Activity
Dagmara Hering, Richard R. Heuser, and Murray Esler
3 Preclinical Model and Histopathology Translational Medicine
and Renal Denervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Yu Sato, Kenichi Sakakura, Maria E. Romero, Frank D. Kolodgie,
Renu Virmani, and Aloke V. Finn
4 Appraisal of Randomized Sham- Controlled Trial Data
on Renal Denervation for the Management of Hypertension . . . . . . . . . . . . . . . . . 37
Stefan C. Bertog, Aung Myat, Alok Sharma, Kolja Sievert, Kerstin Piayda,
Iris Grunwald, Markus Reinartz, Anja Vogel, Iloska Pamela, Natalia Galeru,
Judith Anna Luisa Steffan, Gerhard Sell, Johann Raab, Erhard Starck,
Andreas Zeiher, Wolfgang Stelter, Dagmara Hering, Deepak L. Bhatt,
and Horst Sievert
. . . . . . . . . . . . . . 11
5 Renal Denervation Lowers Blood Pressure in Sham Controlled Studies:
Meta-Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Vasilios Papademetriou, Fotis Tatakis, Panagiotis Tsious,
and Konstantinos Tsious
6 Endpoints for Clinical Effects of Renal Denervation: What Is the Best
Surrogate? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Kevin A. Friede, Marat Fudim, and Paul A. Sobotka
Part II Renal Denervation for Indications Other Than Hypertension
7 An Overview on Hypertension Mediated Organ Damage . . . . . . . . . . . . . . . . . . . 79
Marcio G. Kiuchi and Markus P. Schlaich
8 Renal denervation for Diabetes and Metabolic syndrome . . . . . . . . . . . . . . . . . . . 89
Revathy Carnagarin, Marcio G. Kiuchi, Leslie Marisol Lugo- Gavidia,
and Markus P. Schlaich
9 Renal Denervation for Chronic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Marcio G. Kiuchi, Revathy Carnagarin, Leslie Marisol Lugo Gavidia,
Dagmara Hering, and Markus P. Schlaich
ix
x
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10 Obstructive Sleep Apnea, Resistant Hypertension and Renal Denervation . . . . . 107
Adam Witkowski and Jacek Kądziela
11 Potential Role of Renal Denervation in Management of Atrial Fibrillation . . . . . 113
Tim A. Fischell
12 Potential of Renal Denervation in the Management of Ventricular
Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
Emanuel M. Ebin and Venkatakrishna N. Tholakanahalli
13 Renal Denervation and Kidney Pain Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Leslie Marisol Lugo-Gavidia, Márcio Galindo Kiuchi, Revathy Carnagarin,
and Markus P. Schlaich
Part III Renal Denervation Devices
14 Symplicity SPYRAL™: Device and Procedural Tips and Tricks . . . . . . . . . . . . . . 141
Joachim Weil
15 ReCor Medical Paradise™ System: Device and Procedural Tips and Tricks . . . . 151
Victor Zeijen and Joost Daemen
16 Alcohol-Mediated Renal Sympathetic Neurolysis for the Treatment
of Hypertension: The Peregrine™ Infusion Catheter . . . . . . . . . . . . . . . . . . . . . . . 155
Stefan C. Bertog, Alok Sharma, Dagmara Hering, Felix Mahfoud, Atul Pathak,
Roland E. Schmieder, Kolja Sievert, Vasilios Papademetriou,
Michael A. Weber, Kerstin Piayda, Melvin D. Lobo, Manish Saxena,
David E. Kandzari, Tim A. Fischell, and Horst Sievert
Contents
17 Role of Afferent Nerves in High Blood Pressure and Approaching
Renal Denervation Via the Collecting System: The Verve Medical System. . . . . . 171
Dagmara Hering and Richard R. Heuser
Part IV Measurement of Renal Sympathetic Nerve Activity and Guided
Denervation
18 Sensing Renal Nerve Activity Before, During and After Denervation:
SyMap . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .181
Jie Wang, Yue-Hui Yin, Yue Wang, Wei Ma, and Weijie Chen
Part V New Device-Based Concept for the Diagnosis and Treatment
of Hypertension
19 Transcatheter Carotid Body Denervation: First-in-Man Results
and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Melvin D. Lobo
20 Carotid Baroreceptor Amplification for Treatment of Resistant
Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Wilko Spiering
Part VI Unresolved Topics
21 Patient Selection for Renal Denervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Julien Doublet, Romain Boulestreau, Julie Gaudissard, Philippe Gosse,
and Antoine Cremer
Contents
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xi
22 Testing for Secondary Hypertension and Difficult to Control Patients . . . . . . . . . 217
Omar Azzam, Márcio Galindo Kiuchi, Revathy Carnagarin,
and Markus P. Schlaich
23 Drug Adherence in Hypertension Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Dan Lane, Michel Burnier, and Pankaj Gupta
24 Patient Preference for Therapies in Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Filip M. Szymanski and Anna E. Platek
25 Renal Denervation Cost Analysis and Consideration . . . . . . . . . . . . . . . . . . . . . . . 241
Julie Bulsei and Isabelle Durand-Zaleski
26 What Needs to Be Shown Before Renal Denervation Can Be Used
in Clinical Practice? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Manish Saxena and Melvin D. Lobo
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Part I
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Physiology, Anatomy, Pivotal Hypertension Trials
and Considerations for Trial Design
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