Heart failure has a high morbidity and mortality because the heart is one of the least regenerative organs in the human body. Drug treatments for heart failure manage symptoms but do not restore lost myocytes. Cellular replacement therapy is a potential approach to repair damaged myocardial tissue, restore cardiac function, which has become a new strategy for the treatment of heart failure. The purpose of this study is to assess the safety, feasibility and efficacy of intramyocardial delivery of cardiomyocytes at the time of coronary artery bypass grafting in patients with chronic heart failure.
Patients with heart failure will be treated with allogenic human pluripotent stem cell-derived cardiomyocytes ( hPSC-CM ) from healthy donors. The cells will be injected directly into the myocardium at time of coronary artery bypass grafting. Patients will be assessed at 1, 6 and 12 months after cell transplantation for safety, feasibility and efficacy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
20
Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
HelpThera
Nanjing, Jiangsu, China
Incidence of sustained ventricular arrhythmias
defined as the proportion of patients experiencing ventricular arrhythmias lasting more than 30 seconds
Time frame: 1~6 Month Post-operation
Incidence of newly formed tumors
by comparing chest, abdominal and pelvic CT scan and PET-CT scan
Time frame: 1~12 Month Post-operation
Overall Left Ventricular systolic performance as assessed by MRI
Size of infracted myocardium, left ventricular side wall thickness at diastolic, interventricular septum thickness, left ventricular ejection fraction, left ventricular end-systolic volume and end-diastolic volume, stroke volume, cardiac output, myocardium density and left ventricular mass at diastolic will be evaluated and compared to baseline values.
Time frame: Baseline, 6 and 12 Months Post-operation
Overall Left Ventricular systolic performance as assessed by Echocardiogram
Interventricular septum thickness at diastolic, left ventricular end-systolic diameter and end-diastolic diameter, left ventricular posterior wall thickness at diastolic, left atrial diameter, left ventricular ejection fraction, mitral flow pattern (E/A) will be evaluated and compared to baseline values.
Time frame: Baseline, 6 and 12 Months Post-operation
Overall Left Ventricular systolic performance as assessed by PET/ECT Scan
Myocardium perfusion
Time frame: Baseline, 6 and 12 Months Post-operation
Functional status by 6 minute walk test
Evaluate Functional Capacity via the Six Minute Walk Test
Time frame: Baseline, 6 and 12 Months Post-operation
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Functional status by New York Heart Association (NYHA) Classification
Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination
Time frame: Baseline, 6 and 12 Months Post-operation
Minnesota Living With Heart Failure Questionnaire (MLHFQ)
Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF). The Maximum possible scores being 105 and the minimum 0. Higher scores indicate a worse or worsening quality of life, while lower scores or decreasing scores indicate a better quality of life.
Time frame: Baseline, 1, 6 and 12 Months Post-operation
Incidence of Major Adverse Cardiac Events (MACE)
Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) non-lethal myocardial infraction, and (3) hospitalization for worsening HF
Time frame: Baseline, 1~12 Months Post-operation
Incidence of Serious Adverse Events (SAE)
SAE justified (all undesirable or unintended diseases or laboratory and imaging disorders and symptoms that occur in subjects after CABG surgery and 12 months postoperative follow-up, or until the subject withdrawals from the study. AE grading will be based on Common Terminology Criteria for Adverse Events (CTCAE) V5.0.)
Time frame: Baseline, 1~12 Months Post-operation
Changes in penal reactive antibodies (PRA)
Changes in penal reactive antibodies (PRA) as assessed via blooddraw
Time frame: Baseline, 1, 6 and 12 Months Post-operation
Changes in donor specific antibodies (DSA)
Changes in donor specific antibodies (DSA) as assessed via blooddraw
Time frame: Baseline, 1, 6 and 12 Months Post-operation
Incidence of severe arrhythmia
Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring
Time frame: First month post-operatively
Changes in cytokines
Change in NT-proBNP as assessed via blooddraw
Time frame: Baseline,1, 6 and 12 Months Post-operation