hiPSC-CMs-loaded Chitosan Patch to Treat Severe Chronic Ischemic Heart Disease

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Human Induce Pluripotent Stem Cell-derived Cardiomyocytes(HiCM-188) -Loaded Chitosan Patch to Treat Severe Chronic Ischemic Heart Disease

This is an exploratory study. A total of 16 patients meeting the inclusion and exclusion criteria and awaiting coronary artery bypass grafting (CABG) surgery will be enrolled. After providing informed consent, participants will be randomized 1:1 under double-blind conditions into two groups:

1. CABG + HiCM-188-loaded chitosan patch group (patch size: 2×4 cm; containing 5 million cells per patch)
2. CABG + blank chitosan patch group (identical in appearance but without HiCM-188 cells).

During CABG surgery, investigators will apply two HiCM-188-loaded chitosan patches onto the epicardial surface over regions of hypokinetic myocardium. The total transplanted cell dose per patient in the treatment group is 1 × 10⁷ . In the control group, eight patients will undergo identical surgical procedures with application of chitosan patches without HiCM-188 cells.

Inclusion Criteria:

1. Age between 18 and 80 years (inclusive).

2. Willingness and ability to give written informed consent.

3. Chronic left ventricular dysfunction classified as Stage D (refractory end-stage heart failure) according to ACC staging criteria.

4. NYHA functional class III-IV despite optimized guideline-directed medical therapy for heart failure.

5. Indication for coronary artery bypass grafting (CABG), meeting one of the following anatomical criteria:

   5.1 Class I Indications :

   1. Left ventricular dysfunction with significant left main coronary artery disease;
   2. Left ventricular dysfunction with "left main equivalent" disease (i.e., ≥70% stenosis in proximal LAD or proximal LCx);
   3. Left ventricular dysfunction with two- or three-vessel disease including proximal LAD stenosis.

   5.2 Class IIa Indication : Left ventricular dysfunction with substantial viable, akinetic but revascularizable myocardium, not covered by above Class I anatomical criteria.

6. Left ventricular ejection fraction (LVEF) ≤40% as measured by echocardiography or cardiac MRI within 6 months prior to enrollment (excluding measurements obtained within 1 month post-myocardial infarction).

7. Echocardiographic evidence of regional wall motion abnormalities (hypokinesis, akinesis, or presence of ventricular aneurysm).

Exclusion Criteria:

Patients meeting any of the following criteria are ineligible for study participation:

1. History of permanent pacemaker, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy (CRT) device implantation.
2. Severe valvular heart disease or prior prosthetic valve replacement.
3. Prior percutaneous coronary intervention (PCI) with stent implantation.
4. Chronic atrial fibrillation.
5. History of sustained ventricular tachycardia or aborted sudden cardiac death.
6. Baseline estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m².
7. Hematocrit <25%.
8. Severe contrast media allergy (anaphylactic or life-threatening reaction history).
9. Coagulation disorder (INR >1.5 without therapeutic anticoagulation, platelets <50×10⁹/L, or clinically significant bleeding diathesis).
10. Known hypersensitivity to penicillin or streptomycin.
11. Contraindication to undergoing cardiac MRI (e.g., incompatible implanted devices, severe claustrophobia unresponsive to premedication).
12. History of solid organ or bone marrow transplantation.
13. Active malignancy or history of cancer within the past 5 years (except non-melanoma skin cancer or carcinoma in situ).
14. Life expectancy <1 year due to non-cardiac conditions.
15. Long-term systemic immunosuppressive therapy (e.g., corticosteroids, TNF-α inhibitors).
16. Contraindications to immunosuppressive therapy (e.g., active infection, uncontrolled diabetes, peptic ulcer disease).
17. Active infectious diseases: HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis (Treponema pallidum, TP).
18. Currently participating in another interventional clinical trial.
19. Pregnant or lactating women.