SCS for Vasospastic Angina Vasospastic Angina Pectoris - a Prospective Study

Study Overview
=================
Brief Summary
-----------------
According to the 2020 Dutch guideline on chest pain (AP) without obstructive coronary artery disease, 70% of female and 30% of male patients undergoing a coronary angiogram (CAG), have no obstructive coronary artery disease.In the majority of patients the complaints are based on vascular dysfunction, including epicardial vascular spasms. For patients who are refractory to drug treatment, spinal cord stimulation (SCS) can be a treatment option. SCS is used for the treatment of refractory neuropathic and ischaemic pain. In recent studies the use of SCS is proven for refractory angina pectoris, but the group with refractory vasospastic angina pectoris (rVSA) predominantly seen in women with invalidating impairment of quality of life, is overlooked, as no evidence of obstruction is found at CAG. With this pilot study the investigators hypothesize that SCS is effective in reducing the number and intensity of angina attacks, reducing nitrate use, reducing inhospital treatment and ER presentations, thereby reducing medical costs, and above all, increasing quality of life.

Detailed Description
-----------------
Rationale: Of the patients undergoing a coronary angiogram because of chest pain (AP), 67% of female and 33% of male patients have no obstructive coronary artery disease. In the majority of patients (59-89%) the complaints are based on vascular dysfunction, including epicardial vascular spasms (EVS). For patients who are refractory to drug treatment, spinal cord stimulation (SCS) can be a treatment option. SCS is used for the treatment of refractory neuropathic and ischaemic pain. In recent studies the use of SCS is proven effective for refractory angina pectoris, but the group with refractory vasospastic angina pectoris (rVSA), predominantly seen in women with invalidating impairment of quality of life, is overlooked, as no evidence of obstruction is found at CAG. With this study the investigators hypothesize that SCS is effective in reducing the number and intensity of angina attacks, reducing nitrate use, reducing inhospital treatment and ER presentations, thereby reducing medical costs, and above all, increasing quality of life. Objective: the main objective of this study is to evaluate the clinical effects of SCS on the number and intensity of VSA attacks. Secondary objective is to objectivate the effects of SCS on coronary spasms during the provocative acetylcholine test, and assess medical costs, patient satisfaction and quality of life. Study design: prospective study in two phases. Phase 1: evaluation of clinical effectiveness. Phase 2: evaluation of SCS on vascular spasms during acetylcholine provocation test. Study population: 10 patients with refractory AP due to epicardial vascular spasms. Intervention: implantation with a SCS device with one or two lead(s) in the epidural space of T1 to T4, active electrodes depending on mapping of the painfull area, under local anesthesia and sedation. Acetylcholine provocation test during coronary angiogram at 6 months. Main study parameters/endpoints: primary endpoint is the Seattle Angina Questionnaire (SAQ) at month 1 and 3. Secundary endpoints are presentation at ER, estimated medical costs, and patient satisfaction measured on a 11 point Numeric Rating Scale and quality of life with the EQ5D at month 3, compared to baseline. Endpoints of the acetylcholine test are changes in coronary flow and coronary diameter compared to baseline. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: SCS is proven to be safe for neuropathic and ischaemic pain and is widely used in clinical practice. With the positive results of an ongoing clinical trial for refractory coronary angina, the investigators estimate the efficacy of SCS to be around 80-90% in reducing VSA attacks with 50% after 3 months and therefore very effective in otherwise refractory drug treatment regiments. Furthermore, baseline study parameters will be extracted from the routine questionnaires and during visits to the outpatient clinic. Only in patients who specifically consent to it, an additional acetylcholine test 6 months after SCS implantation during coronary angiography (CAG) is performed. This is an additional coronary angiogram procedure under local anesthesia which potentially provokes VSA. Done by experienced personal this is a safe test with a complication risk of 0-0.7% for severe cardiac complications, comparable to coronary angiogram with functional flow reserve measurement. A potential benefit for the participants is that SCS results in reduction of VSA attacks, reduction of nitrate use, less presentation at an ER, an improved quality of life, and acceptation as standard treatment.

Official Title
-----------------
Spinal Cord Stimulation for Vasospastic Angina Pectoris - a Prospective Study

Conditions
-----------------
Angina Pectoris; Angiospastic

Intervention / Treatment
-----------------
* Device: Spinal Cord Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: VSA is objectivated with a provocative acetylcholine test mentally competent and able to fill in the questionnaires refractory VSA defined as disabling chest pain with a maximum tolerated dosage of calcium antagonists, long acting nitrates, angiotensin converting enzyme inhibitors for a minimum of three months absence of obstructive coronary artery disease evident in a main coronary artery (diameter stenosis<50%, Instant Flow Reserve (IFR) >0.89, or Fractional Flow reserve (FFR) >0.80) able to use the remote control of the SCS system Exclusion Criteria: inability to visit the outpatient department for the follow-up visits unable to provide informed consent myocardial infarction in the previous three months procedures like percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), nor instability of the clinical signs and symptoms of refractory angina in the previous three months implanted pacemaker or implantable cardioverter-defibrillator (ICD) incompatible with SCS indication for ongoing anticoagulation therapy pregnant women and those who are breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: single<br>Subjects are their own control | Device: Spinal Cord Stimulation<br>* Single lead placement in the posterior thoracic epidural space (T1-T4) connected to a subcutaneous battery<br>* Other names: Dorsal Column Stimulation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seattle Angina Questionnaire (SAQ) | For patients with coronary artery disease, the Seattle Angina Questionnaire (SAQ) has emerged as the most commonly used measure of disease-specific health status to quantify patients' symptoms of angina and the extent to which their angina affects their functioning and quality of life. Scores of 0 to 30 translate to daily angina, 31 to 60 to weekly angina, 61 to 99 to monthly angina, and 100 to no angina. | baseline (before implant) - 1 month after implant - 3 months after implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Euroquol Quality of Life questionnaire (EQ5D-5L) | The EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The maximum score of 1 indicates the best health state, by contrast with the scores of individual questions, where higher scores indicate more severe or frequent problems. In addition, there is a visual analogue scale (VAS) to indicate the general health status with 100 indicating the best health status. | baseline (before implant) -1 month after implant - 3 months after implant | 
| Patient satisfaction - Numeric Rating Scale (NRS) 0-10 | 11-point Likert-type scale | 1 month and 3 months after implant | 
| Complications and side effects | Related to SCS | through study completion, an average of 6 months | 
| Acetylcholine provocation test during coronary angiogram | Test to objectivate coronary spasms (compared to baseline) | 6 months after implant | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ANOCA (Angina with Non-Obstructive Coronary Artery disease), Spinal Cord Stimulation, Angina Pectoris