Lower limb peripheral arterial disease (PAD) is common, affecting over 200 million people
worldwide and present in 12 to 14% of the global population (20% over the age of 75 years)1.
The most common symptom is intermittent claudication, a symptom of muscular lower limb pain
brought on by exertion and relieved by rest2.
PAD is the third leading cause of atherosclerotic cardiovascular morbidity, following
coronary artery disease and stroke, yet the natural history of the limb in patients with IC
is relatively benign with 75% of patients finding that symptoms either remain static or are
somewhat improved with no treatment2. It is due to this natural history of the limb that
there is an increasing tendency to manage patients with claudication conservatively (ie.
Non-invasively).
In patients with intermittent claudication, CV prevention and exercise training are the
cornerstones of management3. There is good evidence for enrolment of patients into a
supervised exercise programme, providing bot improved walking distance and quality of life,
yet widespread provision of such programmes are currently not available within the NHS and
further are unlikely to be delivered within the coming years4.
Revascularisation has historically been indicated if daily life activity is severely
compromised by the lower limb symptoms and such revascularisation is primarily performed
endovascularly with balloon angioplasty +/- stent insertion where needed. The ability to
perform endovascular revascularisation is determined by the anatomical location and severity
of the lower limb atherosclerosis. Endovascular interventions work best with short focal
stenoses rather than longer occlusion where surgical revascularisation is the better option2.
Such interventions are invasive and carry risks including risk of amputation and so surgical
revascularisation is now rarely performed for intermittent claudication. Further, there is
now data available that suggests that early invasive revascularisation in patients with
claudication may in the longer term increase the risk of major limb amputation. This means
that there is a cohort of patients who have significant claudication symptoms affecting their
quality of life who are either (i) not offered revasculairsation or (ii) not prepared to
accept the risks of major lower limb revascularisation.
Given this, there is a need to explore further non-invasive methods that could enhance
walking distances in patients with IC and thus improve overall quality of life and overall
cardiovascular fitness without exposing patients to invasive revascularisations.
There has been an increasing focus on the role of neuromodulation in the management of
several chronic diseases5. Neuromodulation is defined as a physiological process which
consists of the alteration of neuronal and synaptic properties by neurons or substances
released by neurons. Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops,
seems to be the best way to exploit brain plasticity for therapeutic purposes.
Vasomotion is believed to play a pivotal role in capillary function and microcirculation.
Based on spontaneous oscillating change of arteriole and venule diameter it has been
theoretically suggested that oscillatory perfusion may be superior to steady-state flow. It
has been shown that continuous electrical stimulation of sympathetic nerves induces a tonic
vasoconstriction6.
Consistently, procedures like lumbar sympathectomy are used to enhance blood supply in
malperfused limbs. Enhanced parasympathetic stimulation may also cause vasodilatation. We
hypothesise that auricular vagus stimulation could modulates afferent parasympathetic
activity and potentially improves microcirculation7.
From a medical viewpoint, neurostimulation techniques do provide several advantages with
respect to conventional drug or invasive surgical treatments:
Specificity: stimulation can be targeted to particular areas avoiding the insurgence of
systemic side-effects, typical of traditional drug therapies;
Safety: neurostimulation techniques are generally well-tolerated and almost devoid of
dangerous side effects;
Flexibility: the treatment can be interrupted at any time. One such device that allows
neurostimulation to be delivered is the DUCEST neurostimulator device. This is a
minimally invasive device that stimulates the afferent branches of the vagus nerve
situated within the outer aspect of the ear lobe. (Fossa triangularis).
Figure 1: Anatomical landmarks within the ear.
Figure 2: The Ducest Medical device.
Figure 3: The application of the Ducest Medical device to the ear.
One study in the UK has looked at the effect of the DUCEST neurostimulator in 30 patients
with the most severe limb ischaemia who had no revascularisation option and has found that
were significant improvements in the size of and flow through the calf arteries. This
corresponded with an avoidance in major limb amputation in 11 of the 30 patients.
No study in the UK has formally assessed the effect of such an intervention on patients with
IC.
There is a large cohort of patient who would potentially benefit from a low risk,
non-invasive intervention aimed at increasing walking distances and improving quality of
life.