Qiao Liang, Zhu Hongwei, Li Yongjie
1. Overview
Angina pectoris is a clinical syndrome caused by acute, temporary ischemia and hypoxia of the myocardium due to insufficient coronary artery blood supply. It is characterized by paroxysmal anterior chest crushing pain, which may be accompanied by other symptoms. The pain is mainly located in the posterior part of the sternum and may radiate to the precordial region and the left upper extremity, often occurring during labor or emotional excitement, lasting several minutes, and disappearing after rest or nitrate preparation. The disease is mostly seen in men, and most patients are over 40 years old. Exertion, emotional excitement, satiety, cold, rainy weather, acute circulatory failure, etc. are common triggers. In most patients with coronary stenosis and exercise-induced myocardial ischemia, angina can be improved by revascularization. Refractory angina pectoris is severe chronic chest pain caused by coronary artery disease that cannot be relieved by coronary bypass, interventional procedures, or medications. With the development of surgical techniques and pharmacological treatments, the survival rate of patients with coronary artery disease has improved significantly in the past decades, which has led to an increase in the number of patients with refractory angina pectoris. The treatment of refractory angina has been a difficult area of clinical and medical research. Several treatment options are available, such as thoracic epidural injection, stellate ganglion blockade, enhanced external conterpulsation, and percutaneous laser revascularization. myocardial laser revascularization, transcutaneous electrical nerve stimulation, and spinal cord stimulation (SCS). Among them, SCS, as one of the important tools of neuromodulation, has received increasing attention in clinical application and scientific research because of its better safety and efficacy. Qiao Liang, Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University
2. Indications
SCS has been used in the treatment of chronic pain since the late 1960’s. It was first reported in the world in 1987 for the treatment of refractory angina pectoris and has been followed by a large number of clinical cases, scientific studies and reviews. It has been recommended by the American College of Cardiology and American Heart Association in their guidelines (class IIb) and by the European Society of Cardiology (therapeutic alternative 1). A recent large meta-analysis by Taylor suggests that SCS has similar efficacy and lower medical costs compared to conventional coronary artery bypass and laser revascularization. A recent large meta-analysis by Taylor suggests that SCS has similar outcomes and lower medical costs than conventional coronary artery bypass and laser revascularization. Other similar studies have suggested that SCS can be selected for medically and surgically refractory angina cases, as well as for patients with angina who are unable or unwilling to undergo coronary artery bypass surgery or interventional procedures. In addition, patients undergoing SCS should have good psychological and cognitive abilities to successfully cooperate with intraoperative and postoperative testing, evaluation, and follow-up.
2. Surgical operation
The patient is mostly in the prone position during surgery. The advantage of choosing local anesthesia is that the surgeon can communicate with the patient during the intraoperative stimulation test to ensure that the tested abnormal sensory area covers the painful area, which is an important indication of good SCS electrode placement and a basic guarantee of good postoperative outcome. During spinal cord electrical stimulation surgery, a 4-point or 8-point electrode is implanted in the epidural space with the upper end to the C7/T1 level under the guidance of X-ray images (Figure 1). During the intraoperative stimulation test, the patient’s sensory abnormalities (parasthesia) may manifest as pins-and-needles pain or numbness that intensifies with increasing stimulation intensity, and coverage varies with the choice of stimulation electrode sites.
Figure 1. X-rays of the patient after implantation of SCS electrodes (head end of electrode is located in the C7/T1 epidural space of the spinal cord). a: frontal, b: lateral. (Source: SH Lee, et al, 2012)
Regarding the spinal cord phase of electrical stimulation, the literature consistently selects C7-T1/T2. In comparison, there is a large variation in stimulation parameters. A common set of stimulation parameters are: frequency 50 Hz, pulse width 270 μs, and intensity at which the patient has no significant pain and numbness (can have slight sensory abnormalities). It is generally accepted that conditions are present for implantation of a pulse generator if the degree and frequency of angina pectoris is reduced by 50% or more with spinal electrical stimulation, the latter usually being implanted in the patient’s left upper abdomen under general anesthesia. The patient can also control the switching and intensity of the stimulator by means of a modulating device.
3. Efficacy and mechanism
There is a large body of literature confirming the effectiveness of SCS in the treatment of refractory angina: reduction in angina attacks, reduction in short-acting nitroglycerin or mononitrate dosage, increased activity tolerance, improvement in ST-segment depression on the ECG, prolongation of walking distance from the 6-minute walk test to the time of angina attack, improvement in quality of life, and reduction in hospitalizations and outpatient visits for heart-related disorders.
Angina is caused by myocardial ischemia, in which chemical or mechanosensory receptors in the heart activate and release prostaglandins, adenosine, bradykinin and other substances. These substances stimulate the terminals of sympathetic and vagal afferent fibers. Specifically, angina is transmitted via visceral afferent nerve fibers to the C7-T5 phase of the spinal cord.
The mechanism of SCS for the treatment of refractory angina may be related to the gating theory: stimulation of A-beta fibers is able to inhibit nociceptive afferents through the posterior horn of the spinal cord. However, more studies suggest that the mechanism of spinal cord electrical stimulation for alleviating chronic refractory angina may be multifactorial, including attenuation of pain perception, reduction of sympathetic excitability, reduction of myocardial blood demand, elevation of coronary microcirculatory flow, and a positive effect on cerebral blood flow.
Attenuation of pain perception: It has been suggested that electrical spinal cord stimulation increases the release of inhibitory interneurons GABA in the spinal cord in the pain sensory pathway, which in turn decreases the release of excitatory neurotransmitters such as glutamate and aspartate. For example, in a rat model, the inhibitory effect of SCS on glutamate and aspartate release was lost when GABAb receptor antagonists were injected locally in the posterior horn of the spinal cord. On the other hand, intrathecal injection of GABAb receptor activator and adenosine receptor activator enhances the effect of SCS. SCS also increases beta-endorphin, which attenuates pain perception.
Reduction of sympathetic excitability: Spinal cord electrical stimulation is cardioprotective not by simply reducing the sympathetic activity of the heart, but by reducing overall sympathetic excitability, thereby reducing the oxygen demand of the heart. In addition, short term myocardial ischemia can also significantly increase the activity of the cardiac nervous system which can lead to arrhythmias. scs can reduce the excitability of neurons in the heart.
Effects on cerebral blood flow: Non-invasive methods such as PET, functional MRI, and magnetoencephalography can be used to study the effects of SCS on cerebral blood flow. It has been found that SCS increases the perfusion of blood in the hypothalamus, the parafascicular gray matter, and the thalamus, while decreasing the perfusion of blood in the posterior insula, which regulates the sympathetic system.
Effects on coronary blood supply: Several studies have demonstrated that SCS reduces angina attacks and short-acting nitrate use, increases patients’ tolerance to exercise, and improves ST-segment depression on the electrocardiogram. Various research tools have shown that SCS reduces catecholamine levels and increases myocardial blood perfusion. For example, Figure 2 shows the increase in myocardial blood supply in an elderly male who underwent SCS (one year follow-up). This patient had a typical history of angina pectoris: severely limited left ventricular function, involvement of three coronary arteries, two myocardial infarctions, two myocardial bypasses, three interventions, and all treatments were tried, but angina attacks were still induced by even mild activity.
Figure 2. Effect of SCS on myocardial blood supply (myocardial blood supply in an elderly male patient undergoing SCS, where a is preoperative and b is 1 year postoperative). Source: E. Fricke, et al, 2009.
However, studies of the effect of SCS on increasing myocardial perfusion have not all been consistent. Sample sizes vary across reports (some are smaller), follow-up intervals vary, and some authors suggest that SCS affects redistribution of blood flow between ischemic and non-ischemic areas of the heart. In conclusion relevant conclusions remain to be confirmed.
In a prospective randomized study comparing the effects of SCS with coronary artery bypass surgery (CAB), SCS (n = 53, 41 men) and CAB (n = 51, 42 men) were comparable in terms of subjective symptom improvement, and the former had a significantly lower mortality rate (SCS: 1, CAB:7). Because patients feel tingling behind the sternum while receiving SCS, a strictly double-blind controlled trial was not actionable.
4. Safety and complications
SCS is an overall safe and effective treatment for refractory angina. There have been numerous studies in recent years to determine whether SCS masks angina and thus increases the risk of infarction, for example, Anderson and colleagues studied 50 patients with SCS over an observation period of 37 months. Ten of these patients had an acute infarction, and nine reported that the pain of the acute infarction was significantly different and more intense than the usual pain and was not affected by SCS. The remaining studies suggest similar results, concluding that SCS does not increase the risk of infarction and may even improve myocardial blood supply.
In addition, SCS is used in patients with severe coronary artery disease, which is often associated with arrhythmias. The application and proper selection of SCS will not affect the installation of permanent pacemakers or implantable defibrillators in these patients.
Regarding complications of SCS procedures, Cameron summarized the literature for the last 20 years, with a total of 2753 patients treated with SCS. The complication rates were 13.2% for electrode dislocation, 9.1% for electrode fracture, and 3.4% for infection. Optimizing the implantation technique and postoperative management can reduce the probability of complications. In a German study (German Angina Register) involving 101 patients, the rates of SCS complications were 5% for electrode dislocation, 5% for electrode fracture, and 3% for infection.
Overall, SCS is a reversible, minimally invasive and safe treatment.
5. Summary
Refractory angina is a specific coronary syndrome caused by microcirculatory disturbances in severe coronary artery disease and endothelial dysfunction.SCS is a relatively safe and effective treatment for refractory angina: it reduces the frequency and extent of angina attacks, decreases the dosage of short-acting nitrates, increases activity tolerance, and reduces the number of hospital admissions for cardiac events. In addition, SCS does not mask myocardial infarction. Some studies suggest that SCS may also improve myocardial blood supply.