48 / 70
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 5, September/October 2019
290
AFRICA
Renal denervation: dark past, bright future?
Marshall Heradien, Felix Mahfoud, Doug Hettrick, Paul Brink
Abstract
The purpose of this review is to update the reader on the
relevance of autonomic nervous system imbalance in clinical
cardiology. Increased sympathetic tone associates with the
metabolic syndrome, hypertension and cardiac arrhythmias.
With the kidneys playing a pivotal role in increased peripheral
resistance, sodium and water retention and other mechanisms,
renal denervation (RD) may theoretically restore autonomic
imbalance and improve cardiovascular outcomes. Landmark
RD trials and novel uses for RD in cardiac arrhythmia
management are discussed.
Keywords:
autonomic imbalance, hypertension, hypertensive
heart disease, atrial fibrillation, renal denervation
Submitted 18/2/19, accepted 22/7/19
Cardiovasc J Afr
2019;
30
: 290–296
www.cvja.co.zaDOI: 10.5830/CVJA-2019-045
What is autonomic imbalance?
The autonomic nervous system consists of a sympathetic and
parasympathetic system. Autonomic imbalance (AI) defines
a state of relatively increased sympathetic tone (IST) and/or
decreased parasympathetic tone. AI is associated with many
disease components including heart failure, atrial fibrillation,
obesity and chronic kidney disease.
1-4
Our modern lifestyle of
high stress levels, reduced exercise and poor diets rich in salt and
carbohydrates undoubtedly fuels both the metabolic syndrome
and AI.
AI and sudden cardiac death
Interestingly, AI is also associated with sudden cardiac death
(SCD) during severe emotional stress.
5
Congenital long-QT
syndrome also illustrates this association particularly well.
6
Symptomatic mutation carriers typically experience syncope
and sometimes SCD during situations associated with IST, such
as excitement, swimming or exercise. Conversely, higher resting
vagal tone seems to be protective, and anti-sympathetic therapy
such as beta-blockers or left cardiac sympathetic denervation
(LCSD) are established therapies for this inherited cardiac ion
channelopathy.
Another example where AI was associated with and even
predicted SCD, came from a prospective cohort of apparently
healthy young male French civil servants.
7
Here, Jouven and
co-workers used exercise-related heart rate profiles as surrogate
markers of cardio-autonomic tone. They found that faster
resting heart rate (
>
75 bpm), indicative of IST, and slower post-
exercise recovery of heart rate (
<
25 bpm), indicating reduced
parasympathetic tone, were associated with a significantly higher
SCD risk later in life.
The kidneys play a central role in autonomic
dysfunction
With the kidneys playing a pivotal role in increased peripheral
resistance, sodium and water retention and other mechanisms,
renal denervation (RD) may theoretically restore autonomic
imbalance and improve cardiovascular outcomes.
8
Innovative
endovascular techniques provide minimally invasive access to
reduce sympathetic brain–kidney cross-talk, which may restore
AI and prevent its associated complications.
Renal nerve supply: anatomy and physiology
Anatomical and physiological knowledge of the renal nerve
supply supports the hypothesis that RD should lower blood
pressure and consequently produce beneficial cardiac effects.
9
The afferent renal nerves, mostly located in the renal pelvis,
transmit signals via the dorsal spinal cord to the brain when
activated by stretch forces (Fig. 1). Activated centres in the
brain include the nucleus tractus solitarius, medulla oblongata
and paraventricular hypothalamic nuclei. These signals increase
vasopressin and oxytocin release, accompanied by increased
activation of efferent sympathetic neurons. These neurons run
along paravertebral ganglia and large blood vessels, where
they exit to vital organs located in the thoraco-lumbar region.
In the thorax, sympathetic nerves terminate in the sino-atrial
node, atrio-ventricular node and ventricles. Here, sympathetic
stimulation increases chronotropy, dromotropy and inotropy,
Department of Internal Medicine, Stellenbosch University,
Cape Town, South Africa
Marshall Heradien, MB ChB, BSc Hons, MMed, Cert Cardiology,
hartspesialis@gmail.comPaul Brink, MB ChB, MMed, PhD
Klinik für Innere Medizin III, Saarland University Hospital,
Homburg, Saarland, Germany
Felix Mahfoud, MD, PhD
Coronary and Renal Denervation, Medtronic, Santa Rosa,
CA 95403, United States of America
Doug Hettrick, PhD
Review Article