Closed-loop brain neurofeedback on the left prefrontal cortex to lower stress-related heart responses in people with coronary heart disease and anxiety.

Closed-Loop Neurofeedback Targeting the Left Dorsolateral Prefrontal Cortex for Cardiac Autonomic Modulation in Coronary Artery Disease With Anxiety - A Randomized, Sham-Controlled Trial (HEART-SET-2)

This trial will test whether closed‑loop fNIRS neurofeedback aimed at the left dorsolateral prefrontal cortex can lower heart rate during a cold‑pain stress test in adults with stable coronary heart disease and anxiety.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shenyang Medical College (Academic / other)
• Locations: 1 site (Shenyang, Liaoning)
• Trial ID: NCT07244484 on ClinicalTrials.gov

What this trial studies

This exploratory interventional trial uses real‑time fNIRS-based closed‑loop neurofeedback to train left dorsolateral prefrontal cortex (DLPFC) activation in adults with stable coronary heart disease and comorbid anxiety. Participants receive either real left DLPFC neurofeedback or a sham control while undergoing standardized cold‑induced pain stress, and baseline‑corrected heart rate during the stress window is the primary physiological outcome. The study also measures participants' ability to volitionally upregulate left DLPFC activation, interhemispheric DLPFC synchronisation, and records adverse events during training and experimental sessions. Analyses will test whether changes in heart rate are associated with and partly mediated by changes in DLPFC activation or interhemispheric synchrony.

Who should consider this trial

Good fit: Adults over 18 with confirmed stable coronary heart disease, a DSM‑5 anxiety disorder, right‑handedness, resting heart rate 60–100 bpm, HAMA score ≥16 and HAMD‑17 score ≤17 who can attend site visits and tolerate fNIRS and cold‑pressor testing are ideal candidates.

Not a fit: Patients with unstable cardiac conditions (for example acute unstable angina, severe congestive heart failure NYHA class IV), atrial fibrillation, significant valvular disease, unstable blood pressure, or those unable to undergo fNIRS or cold‑pain testing are unlikely to receive benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could reduce stress‑related heart rate surges and improve cardiac autonomic regulation in people with coronary heart disease and anxiety.

How similar studies have performed: Preliminary neurofeedback work in healthy and psychiatric samples has shown some ability to change prefrontal activity and autonomic markers, but closed‑loop fNIRS neurofeedback specifically targeted to left DLPFC in coronary heart disease with anxiety is largely novel and unproven.

Eligibility criteria

Inclusion Criteria:

* Age \>18 years, any sex.
* Right-handed, with resting heart rate between 60 and 100 beats per minute.
* Confirmed diagnosis of CHD, defined as at least one of the following:

  (i) positive stress test; (ii) documented myocardial infarction (MI) with electrocardiographic changes and concurrent elevation of creatine kinase MB isoenzyme or troponin; (iii) angiographically confirmed coronary atherosclerosis with ≥50% stenosis in at least one coronary artery.
* Diagnosis of an anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
* Hamilton Anxiety Rating Scale (HAMA) score ≥16 and 17-item Hamilton Depression Rating Scale (HAMD-17) score ≤17.

Exclusion Criteria:

* Acute unstable angina.
* Severe congestive heart failure (New York Heart Association \[NYHA\] class IV).
* Valvular heart disease.
* History of atrial fibrillation.
* Unstable blood pressure, defined as systolic blood pressure \>180 mmHg or \<90 mmHg.
* Pregnancy.
* History of unstable medical conditions, including cerebrovascular disease, dementia, hyperthyroidism, pulmonary disease, or malignancy. These are assessed through medical history, electronic health records, physical examination, and ECG findings.
* High risk of suicide or homicide.
* Presence of other psychiatric disorders, including psychotic disorders, bipolar disorder, or active substance use disorders.
* Use of psychotropic medication within 1 month prior to enrolment, to avoid potential interference with haemodynamic measurements.

Where this trial is running

Shenyang, Liaoning

• Second Affiliated Hospital of Shenyang Medical College — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Principal investigator: Lin Tao, MM — Shenyang Medical College
• Study coordinator: Lin Tao, MM

Conditions Coronary Heart Disease; Anxiety Disorders; Coronary heart disease; Anxiety; Neurofeedback; the dorsolateral prefrontal cortex