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Management of Angina Pectoris: The

Role of Spinal Cord Stimulation

Progress in prevention as well as drug and interventional therapy has
improved the prognosis of patients with cardiovascular disorders. Many
patients at risk have advanced coronary artery disease (CAD), have had
multiple coronary interventions, and present with significant co-morbidity.
Despite adequate risk factor modulation and often several revascularization
procedures, some of these patients still have refractory angina pectoris.
Apart from advanced CAD and insufficient collateralization, the cause is often
endothelial dysfunction. For this situation, one treatment option is
neuromodulation. Controlled studies suggest that, in patients with chronic
refractory angina pectoris, spinal cord stimulation (SCS) provides a relief
from symptoms equivalent to that provided by surgical therapy, but with
fewer complications and lower rehospitalization rates. SCS may result in
significant long-term pain relief with improved quality of life. In patients with
refractory angina undergoing SCS, some studies have shown not only a
symptomatic improvement, but also a decrease in myocardial ischemia and
an increase in coronary blood flow. Discussion is ongoing as to whether this
is a direct effect on parasympathetic vascodilation or merely a secondary
phenomenon resulting from increased physical activity following an
improvement in clinical symptoms. Results from nuclear medical studies
have sparked discussion about improved endothelial function and increased
collateralization. SCS is a safe treatment option for patients with refractory
angina pectoris, and its long-term effects are evident. It is a procedure
without significant complications that is easy to tolerate. SCS does not
interact with pacemakers, provided that strict bipolar right-ventricular
sensing is used. Use in patients with implanted cardioverter defibrillators is
under discussion. Individual testing is mandatory in order to assess optimal
safety in each patient.
Therapeutic options for the management of angina pectoris in patients with
coronary artery disease (CAD) have improved over the past 2 decades.
Nevertheless, angina pectoris is a common and important symptom affecting
many patients with CAD, as well as some with endothelial dysfunction.
Despite optimal drug therapy and no option for coronary revascularization
procedures (percutaneous coronary intervention [PCI] or aortocoronary
bypass [ACB]), some patients with CAD have persistent angina pectoris class
III or IV according to the Canadian Cardiovascular Society (CCS). The
treatment of these patients with non-responding angina pectoris presents a
medical challenge. We have no accurate figures on the occurrence and
frequency of refractory angina, nor is the prevalence of angina pectoris
known in most communities. The overall prevalence of patients referred for
coronary angiography with refractory angina varies from 5% to 15%.
Various treatment concepts have been developed for patients with therapy-
resistant angina pectoris and have been applied in clinical studies: long-term
intermittent urokinase therapy, surgical and percutaneous transmyocardial
laser revascularization, enhanced external counterpulsation, percutaneous in
situ coronary venous arterialization, and transcutaneous electrical nerve and
spinal cord stimulation (SCS). The latter has been established as the most
applicable. It is recommended as the therapy of choice by the European
Society of Cardiology Joint Study Group on the Treatment of Refractory
In this article, we review the role of SCS in the management of severe angina
pectoris in patients with ischemic heart disease and endothelial dysfunction.
Stable and Refractory Angina Pectoris
Endothelial dysfunction is usually diagnosed in the presence of angina
pectoris without obstructive CAD and coronary artery spasm. Patients with
such a diagnoses experience typical anginal chest pain and experience
positive exercise stress testing. About 15-20% of patients undergoing cardiac
catheterization for the assessment of typical chest pain have these
characteristics, and most of them have a good prognosis.
Endothelial dysfunction often marks the onset of atherosclerosis, stays with
the patient for the rest of his or her life, and at the end-stages of CAD
following PCI, causes higher rates of relapse and re-intervention. Endothelial
dysfunction can be ascertained invasively and non-invasively. After
excluding hemodynamically relevant epicardial stenoses by determining the
fractional flow reserve (FFR), the functional status of a coronary artery can
be determined by coronary flow reserve (CFR). As a non-invasive procedure,
ammonia positron emission tomography (PET) and flow-mediated dilatation
of the brachial artery (FMD) can be used.
The survival of patients with CAD is increasing as a result of improved
prevention and coronary intervention, which in turn is leading to an increase
in the prevalence of patients with refractory angina pectoris.
It is important to underline that angina pectoris is a clinic diagnosis.
Imbalance in myocardial oxygen demand and supply can produce myocardial
ischemia. This may cause angina pectoris and lead to a reduction in left-
ventricular contractility, as well as cause arrhythmia, myocardial infarction,
and possibly death. Angina pectoris is commonly due to atherosclerosis of
the coronary arteries, but it can also occur in conjunction with endothelial
dysfunction due to insufficient coronary vasodilatation.
Anti-anginal drug therapy improves the imbalance of the myocardium by
interacting with heart rate, cardiac pre- and afterload, as well as coronary
vascular tone. Hemodynamically significant coronary stenoses with and
without angina pectoris may be dilated (PCI) or operated on (ACB).
Refractory angina pectoris (CCS class III and IV) is a chronic condition
characterized by the presence of angina due to coronary insufficiency in the
co-presence of CAD that cannot be controlled by a combination of medical
therapy, angioplasty, and coronary bypass surgery. Patients with endothelial
dysfunction can also experience refractory angina.
Before selecting patients with refractory angina for SCS, a re-evaluation of
their medical therapy is required in order to ensure an optimal treatment
regimen. Myocardial ischemia should be present, and other causes of chest
pain, such as musculoskeletal pain, esophageal reflux, gastrointestinal
disorder, pericardial disease, vascular disease (aortic dissection, pulmonary
embolism), infection, panic disorder, and pulmonary conditions that cause
chest pain, must be excluded.
Pharmacologic Therapy
The therapeutic options for endothelial dysfunction and stable CAD are
comparable and aim at correcting the imbalanced redox potential. Treating
the classical risk factors with lifestyle modification and drug therapy has
facilitated the successful prevention of clinical cardiovascular events and has
prolonged life expectancy.
In many randomized studies, a reduction in increased low-density lipoprotein
cholesterol and triglyceride, as well as an increase in reduced high-density
lipoprotein cholesterol have contributed to stabilizing plaque, have
frequently demonstrated a regression of coronary atherosclerosis, and have
improved endothelial function. Controlling hypertension, cessation of
smoking, increasing physical activity, and reducing weight all help to halt the
progress of atherosclerosis and to reduce acute events. Lifestyle changes in
the form of increased physical activity with or without weight reduction
frequently lead to a reduction in angina pectoris and improved myocardial
perfusion. In randomized studies, it was possible to show that, compared
with coronary intervention (PCI), increasing physical activity resulted in a
better event-free survival rate, a higher exercise capacity, and a higher
oxygen uptake, and was more cost effective; it achieved clinical
improvement in CCS class I at half the total cost of the interventional
Effect on Cerebral Blood Flow. Non-invasive techniques for determining
cerebral perfusion and measuring functional activity (e.g. PET, functional
MRI, or magnetoencephalography) have contributed to a better
understanding of cerebral function in healthy subjects and in those with
various diseases and the ways in which cerebral function can be influenced
through interventions. Changes in regional blood flow in areas involved with
nociception and cardiovascular control have been documented in patients
treated with SCS for refractory angina. The cerebral areas demonstrating a
relative increase or decrease in CBF could possibly be determined by the
underlying disease (pain during clinical examination, one-sided or two-sided
for paired organs) and the measuring methods, as well as the type of
intervention. In patients with documented CAD, typical anginal and ischemic
electrocardiographic changes can be triggered during dobutamine infusion.
Dynamic PET examinations during induced ischemia reveal increased and
decreased regional CBF. During SCS, increased and decreased regional CBF
can also be observed with and without stimulation in patients with refractory
angina. In these two different patient groups, there are correlations within
the following regions: increased CBF in the hypothalamus, and in the
periaqueductal grey area and bilaterally in the thalamus, and decreased CBF
in the posterior insular cortex, an area that modulates sympathetic effects.
The well supported effects of SCS are possibly attained by influencing central
structures within the area of pain perception and processing. The thalamus
may act as a filter for afferent pain signals.
Effect on Coronary Blood Flow. SCS has repeatedly demonstrated an anti-
anginal effect by reducing angina pectoris and the use of short-acting
nitrates, increasing exercise tolerance, and decreasing ST-segment
depression on the electrocardiogram. Discussion about the effect of SCS on
myocardial blood flow is ongoing.
Angina pectoris is a projected pain that is caused by insufficient perfusion of the
myocardium due to significant coronary stenoses or reduced vasodilatatory
capacity, particularly of the microcirculation. CAD is frequently accompanied by
endothelial dysfunction. In the majority of patients with significant coronary
stenoses and exercise-induced ischemia, pain relief can be achieved following
revascularization and/or through risk factor modulation with improvement in
endothelial function. TENS and SCS are recognized therapies in patients with
refractory angina pectoris. In many clinical studies, the effectiveness of these
therapies have been demonstrated in patients (approximately 2500) with CAD and
endothelial dysfunction: fewer angina pectoris episodes and less short-acting
nitroglycerin (glyceryl trinitrate) or mononitrate intake per time period; increase in
exercise tolerance, time to angina, and the appearance of ST-segment depression;
extended walking distance in the 6-minute walk test before onset of angina;
improvement in quality of life; and fewer stays in hospital as well as visits to the
physician due to cardiac-related symptoms.

Refractory angina pectoris during end-stage CAD and with endothelial

dysfunction is a specific coronary syndrome that is chiefly caused by
microcirculatory disturbances. Already receiving the best use of evidence-
based therapies and with no interventional options, these patients can
benefit from SCS. SCS is safe and effective for treating refractory angina
pectoris - reducing both the number of anginal episodes and the intensity of
the angina pectoris. With SCS the dosage of short-term effective nitrates per
time period is reduced. The work period during exercise tests is significantly
prolonged. SCS leads to a significant reduction in hospital admission for
cardiac causes, without masking myocardial ischemias or myocardial
infarction. The implantation costs are balanced out by savings in aftercare
(fewer consultations and hospital stays).
SCS is an excellent alternative for patients at an increased risk of requiring
operative revascularization. For patients with refractory angina who are
waiting for heart transplantation, SCS is also a good bridging option.
In small studies, an improvement in myocardial blood flow in vital ischemic
myocardial areas has also been proved. It has yet to be investigated whether
SCS, in addition to a proven improvement in symptoms, also reduces