Percutaneous Intracoronary Cellular Cardiomyoplasty for Nonischemic Cardiomyopathy: Clinical and Histopathological Results: The First-in-Man ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) Trial

Abstract

To the Editor: Stem cell therapy has shown potential benefit in heart failure caused by ischemic heart disease (1). There is no data on the role of stem cell therapy in nonischemic dilated cardiomyopathy. We undertook a pilot study of intracoronary stem cell implantation in patients with dilated cardiomyopathy.From a cohort of 44 patients, 24 were randomly allocated to the stem cell therapy arm and 20 to the control arm. All patients were having dilated cardiomyopathy with an ejection fraction (EF) of Յ35%, were New York Heart Association (NYHA) functional class II or more symptomatic for more than 6 months, had normal coronary arteries, and had no other comorbidities such as chronic renal or liver failure or any malignancy.Patients in the treatment arm underwent bone marrow aspiration (50 to 60 ml) from the iliac crest. Mononuclear cells were separated from the bone marrow using Ficoll density gradient separation. The mononuclear cells constituted 89 Ϯ 2% of the cells, were 28 Ϯ 16 million /ml, and CD 34ϩ cells were 1.6 million/ml. The viability of these cells was 99 Ϯ 1%. The patients then underwent right heart catheterization and endomyocardial biopsy from the right side of the interventricular septum. The coronary sinus was then engaged using a Swan-Ganz catheter (Arrow International, Reading, Pennsylvania) that was passed up the coronary sinus, and the balloon was inflated. This was done so that the coronary circulation was slowed and the stem cells would get more time to transmigrate into the myocardium. Once the coronary sinus catheter was inflated, the stem cells were slowly injected into the coronary arteries by hooking the arteries with a Judkins catheter. Two-thirds of the mononuclear cell concentrate was injected into the left coronary artery and one-third was injected into the right coronary artery. The coronary sinus balloon was kept inflated for 3 min during the intracoronary injection. The patients were kept under monitoring for 24 h with electrocardiographic monitoring and serial cardiac enzymes. Follow-up was done at 1 week, 1 month, and then every 3 months for 1 year. At 3 months, Holter monitoring, an echocardiogram, and an endomyocardial biopsy were repeated. An echocardiogram was also repeated at 1 year. Left ventricular function assessment was performed offline by the modified Simpson method by 2 observers blinded to the underlying treatment. All patients were on the maximum tolerated doses of angiotensin-converting enzyme inhibitors and beta-blockers. Diuretic doses (including frusemide and torsemide, and spironolactone) were adjusted to ensure the absence of pedal edema. Informed consent was obtained from all patients, including control patients. The end points of the study were: 1) change in NYHA functional class, 2) a change in left ventricular function, 3) mortality, and 4) endomyocardial biopsy and histopathologic evaluation.Continuous variables were compared by a Wilcoxon 2-sample test (for within-group differences) and the Mann-Whitney U test (between-group differences). Differences...

A safety and feasibility study of cell therapy in dilated cardiomyopathy

“…Furthermore, Seth et al (19) have reported identical mortality in a cell therapy trial for patients with non-ischemic dilated cardiomyopathy. Considering the time interval between the procedure and the occurrence of deaths by pulmonary edema and cardiogenic shock, the severity of the heart failure of the patients at enrollment and the natural history of the disease, we consider these deaths most likely not to be related to the cell injection procedure.…”

“…No adverse events have been reported in a trial where mononuclear cells were delivered to the coronary arteries in 24 patients after coronary sinus occlusion (19). Another trial used the intramyocardial route to deliver cells during thoracotomy, but only 5 IDC patients were included in the trial that reported 7 episodes of ventricular fibrillation during the procedure and 2 deaths by the same mechanism during the perioperative period (18).…”

“…Very few studies have applied cell therapy to patients with non-ischemic dilated cardiomyopathy (18)(19)(20)(21), and conflicting results as to the safety of the procedure have been reported.…”

Endothelial progenitor cells: Implications for cardiovascular disease

“…And indeed, MSC transplantation was associated with significantly increased capillary density and decreased collagen volume fraction in the myocardium, resulting in an improved cardiac function. The first-in-man study was performed by Seith et al (121). Forty-four patients with an ejection fraction 35%, normal coronary arteries, and New York Heart Association (NYHA) functional class II or more were randomly assigned to a stem cell therapy arm (24 patients) or a control arm (20 patients).…”

Stem Cell Therapy for Heart Disease

“…Both demonstrated improved EF. 87,88 Cell Type Comparisons ASC had favorable results in APOLLO and PRECISE. Both trials demonstrated the efficacy of ASC in AMI and left ventricular dysfunction in settings of marked myocardial ischemia.…”