This exploratory, single-center, open-label clinical trial assesses the safety, tolerability, and potential efficacy of a single 5 mg dose of HM2002 injection administered via multiple-point epicardial injections for treating ischemic heart failure. Three patients aged 18-80 undergoing elective coronary artery bypass grafting (CABG) surgery will participate. Using a sentinel dosing approach, the first subject will receive HM2002, followed by a 14-day safety observation before dosing the remaining participants. If any serious adverse events or dose-limiting toxicities occur in the first subject, a Safety Review Committee will evaluate the safety data to determine whether to continue or terminate the trial.

This study is a prospective, single-center, single-dose, open-label investigator-initiated exploratory clinical trial (IIT study) designed to evaluate the safety, tolerability, and potential clinical efficacy of the exploratory dose HM2002 injection administered via single-dose, multiple-point injections through the epicardium for the treatment of ischemic heart failure. The study plans to enroll three patients aged between 18 and 80 years who are scheduled to undergo elective coronary artery bypass grafting (CABG) surgery and have ischemic heart failure. Eligible patients will become study subjects after providing full written informed consent and successfully passing the inclusion and exclusion criteria screening. The exploratory dose for this trial is 5 mg HM2002 injection. The three subjects will be dosed following the sentinel dosing principle. Specifically, after the first subject completes dosing, there will be a minimum interval of 14 days (2 weeks) to confirm safety and tolerability before enrolling the remaining two subjects. If any serious adverse event (SAE) or dose-limiting toxicity (DLT) occurs in the first subject, a Safety Review Committee (SRC) meeting will be convened to review all collected safety data. The committee will then determine whether to proceed with the enrollment of subsequent subjects or terminate the trial.

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria:

1. be ≥18 and ≤80 years of age at the time of signing the informative and be of either sex;
2. have ischemic heart failure (IHF) with left ventricular ejection fraction (LVEF) ≤50% by echocardiography (ECHO), New York Heart Association (NYHA) cardiac function class 3-4, and be proposed to undergo elective coronary artery bypass grafting (CABG);
3. voluntarily sign the informed consent form and fully understand the content, process and possible adverse reactions of the trial. Be able to complete the study according to the requirements of the trial protocol and have good compliance;

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from this study:

1. subjects with the following concomitant symptoms or diseases:

   1. ECHO-confirmed LVEF ≤ 20%;
   2. History of malignant arrhythmias (including multiple ventricular pre-systole, premature ventricular dystocia, tricyclic rhythm, or ventricular tachycardia) manifesting symptomatically or requiring treatment (CTCAE grade 3);
   3. atrial fibrillation (including paroxysmal atrial fibrillation);
   4. Long QT syndrome;
   5. Estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2; f. Serum gammaglutamyl (GGT) ≤ 1.5 mL/min/1.73 m2
   6. Serum alanine aminotransferase (ALT) or aminotransferase (AST) > 3 x upper limit normal (ULN) and total bilirubin (TBIL) > 2 x ULN or more;
   7. Severe coagulation disorders, bleeding disorders, etc;
   8. history of active human immunodeficiency virus (HIV), active hepatitis C virus (HCV), or active hepatitis B virus (HBV); active HIV, HCV, and HBV infections are defined as:
   1. HIV antibody positive;
   2. Anti-HCV antibody and positive for HCV RNA;
   3. HBsAg positive and HBV DNA ≥1000 cps/ml (or 200 IU/ml); i. current malignancy, or a history of malignancy.

2. need for concurrent cardiac or non-cardiac interventional or surgical procedures other than CABG (e.g., valve surgery, ventricular wall tumor surgery, peripheral arterial stenting or surgery)

3. patients with prior systemic or cardiac therapy with similar nucleic acid medications

4. a known history of drug abuse or drug allergy

5. pregnant or lactating women or those who are not using effective contraception;

6. other circumstances judged by the investigator to be inappropriate, such as the investigator's judgment that the subject may be exposed to substantial safety risks, or interference with the results of the study, or lack of participation in completing this trial in accordance with the study protocol.