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 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, 3, 6 and 12 months after cell transplantation for safety 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. 100 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
Coronary artery bypass grafting surgery only.
Shanghai east Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGIncidence of serious adverse events(SAEs) within 1 month post-CABG surgery.
Incidence of serious adverse events(SAEs) within 1 month post-CABG surgery. These include death, fatal myocardial infarction, stroke, cardiac tamponade, cardiac perforation, hemodynamic ventricular arrhythmias (duration \> 15s), and new allogeneic human neoplasms.
Time frame: 1 Month Post-operation
Size of infracted myocardium assessed by MRI
Size of infracted myocardium;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Left Ventricular systolic performance as assessed by MRI
left ventricular side wall thickness at diastolic; interventricular septum thickness;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Left ventricular ejection fraction assessed by MRI
left ventricular ejection fraction;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Overall Left Ventricular systolic performance as assessed by MRI
left ventricular end-systolic volume and end-diastolic volume; stroke volume;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Cardiac output assessed by MRI
cardiac output;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Myocardium density assessed by MRI
myocardium density;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
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Left ventricular mass assessed by MRI
left ventricular mass at diastolic;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Overall Left Ventricular systolic performance as assessed by Echocardiogram
Interventricular septum thickness at diastolic; left ventricular posterior wall thickness at diastolic;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Left Ventricular systolic performance as assessed by Echocardiogram
left ventricular end-systolic diameter and end-diastolic diameter; left atrial diameter;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Left ventricular ejection fraction assessed by Echocardiogram
left ventricular ejection fraction;
Time frame: Baseline, 1, 3, 6 and 12 Months Post-operation
Mitral flow pattern (E/A) assessed by Echocardiogram
mitral flow pattern (E/A) ;
Time frame: Baseline, 1, 3, 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, 1, 3, 6 and 12 Months Post-operation
Functional status by New York Heart Association (NYHA) Classification
Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination. It classifies patients in one of four categories based on their limitations during physical activity; Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.
Time frame: Baseline, 1, 3, 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, 3, 6 and 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, 1~12Months Post-operation
Incidence of severe arrhythmia
Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring
Time frame: First month post-operatively
Changes in penal reactive antibodies (PRA)
Changes in penal reactive antibodies (PRA) as assessed via blooddraw
Time frame: Baseline, 1, 3, 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, 3, 6 and 12 Months Post-operation
Changes in cytokines
Change in NT-proBNP as assessed via blooddraw
Time frame: Baseline,1, 3, 6 and 12 Months Post-operation