This study is a prospective, randomized, sham-controlled, participant- and assessor-blinded, parallel-group clinical trial designed to evaluate the clinical efficacy, mechanistic effects, and safety of right dorsolateral prefrontal cortex (DLPFC) closed-loop functional near-infrared spectroscopy brain-computer interface (fNIRS-BCI) neurofeedback in patients with high-ischaemic-risk chronic coronary syndrome (CCS) and comorbid anxiety disorder. Participants will be randomly assigned in a 1:1 ratio to active neurofeedback or sham feedback. The intervention consists of 4 weeks of treatment, with 20 sessions in total (1 session per weekday, approximately 20 minutes per session). The primary endpoint is the between-group difference in Hamilton Anxiety Rating Scale (HAMA) score at 3 months after treatment. Secondary endpoints include HAMA score and HAMA response rate at the end of treatment, as well as neurophysiological measures collected during Session 1, including right DLPFC activation, heart rate (HR), and heart rate variability (HRV). Exploratory long-term follow-up will assess cardiovascular and bleeding outcomes through 4 years after randomization.
Inclusion Criteria
- Participants will be aged 18 years or older and will provide written informed consent.
- Participants will have chronic coronary syndrome (CCS) with prior coronary stent implantation more than 6 months before enrollment.
- Participants will meet high ischemic risk (HIR) criteria by either of the following:
- Percutaneous coronary intervention (PCI) performed more than 6 months earlier for acute coronary syndrome (ACS), including unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, with implantation of at least 1 coronary stent; or
- PCI performed more than 6 months earlier for a non-ACS indication, together with at least 1 of the following risk factors:
- diabetes mellitus;
- diffuse multivessel coronary artery disease involving all 3 major coronary vessels;
- chronic kidney disease with creatinine clearance less than 50 mL/min (recommended to be calculated using the Cockcroft-Gault formula);
- prior stent thrombosis;
- peripheral arterial disease;
- complex PCI, defined by at least 1 of the following:
- only patent remaining coronary vessel or left main coronary artery stenting;
- implantation of at least 3 stents or treatment of at least 3 lesions;
- bifurcation lesion treated with a 2-stent strategy;
- total stent length greater than 60 mm;
- PCI for chronic total occlusion.
- Participants will meet DSM-5 diagnostic criteria for an anxiety disorder, confirmed by structured psychiatric interview.
- Participants will have a Hamilton Anxiety Rating Scale (HAMA) score of 16 or higher.
- Participants will have a 17-item Hamilton Depression Rating Scale (HAMD-17) score lower than 17.
- Participants will not have used psychotropic medication, including antidepressants, anxiolytics, or antipsychotics, within 1 month before enrollment; prior psychotropic medication use will not itself exclude participation, provided that a washout period has been completed before enrollment and the medication history is documented.
Exclusion Criteria
- Participants will be excluded if they have severe congestive heart failure (New York Heart Association class IV).
- Participants will be excluded if they have moderate-to-severe valvular heart disease.
- Participants will be excluded if they have a history of atrial fibrillation.
- Participants will be excluded if they have unstable blood pressure, defined as systolic blood pressure greater than 180 mmHg or less than 90 mmHg.
- Participants will be excluded if they are pregnant or breastfeeding.
- Participants will be excluded if they have active or recent (within 6 months) severe systemic disease, including any of the following:
- cerebrovascular disease, including stroke or transient ischemic attack;
- dementia or severe cognitive impairment;
- hyperthyroidism;
- active pulmonary disease;
- active malignant tumor.
- Participants will be excluded if they have suicidal or homicidal risk based on clinical interview.
- Participants will be excluded if they have other severe psychiatric disorders, including but not limited to:
- psychotic disorders, such as hallucinations or delusions;
- bipolar disorder.