Abstract
Heart failure (HF), continuing to be a notable cause of morbidity and mortality worldwide, also is a noteworthy economic burden to the patients. Current medical management of HF has poor efficacy to completely arrest or reverse the progression to end-stage disease. As the option of cardiac transplantation remains limited to few patients, the stem cell approach continues to be a promising one in developing a novel therapy in the treatment of HF.This review attempts to discuss and compare the outcomes of numerous clinical trials that involved treatment of HF of variable etiologies with stem cells of numerous lineages such as bone marrow-derived cells (BMCs), mesenchymal stem cells (MSCs), cardiosphere derived progenitor cells (CDCs), etc. We reviewed articles and randomized controlled trials (RCT) that used stem cells to treat heart failure. The articles and RCT studies were obtained through a search on PubMed and Medline databases and performed using regular and medical subject heading (MeSH) keyword search strategy. A total of 17 trial-based studies, along with other articles that met the aim of the review, were selected. A discussion of the findings from major clinical trials such as the C-CURE, CHART-1, POSEIDON, POSEIDON-DCM, TAC-HFT, and other small scale trials highlights the change in functional and mechanical parameters of HF, namely, left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), end-systolic volume (ESV), 6-minute walking test distance (6MWTD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and assessment of New York heart association (NYHA) class of heart failure, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score to reflect improvement in quality of life (QoL) of patients.Out of the studies analyzed, the majority reported significant improvements in at least two of the parameters mentioned above. However, more phase three randomized trials are required to compare the efficacy of multiple lineages of stem cells, factoring in molecular and dosage factors to develop a standardized therapy.
Highlights
BackgroundDespite the recent advances in medical therapy, Heart Failure (HF) remains a significant cause of mortality and morbidity worldwide
Current therapies to manage HF include combined drug therapies, left ventricular assist devices (LVAD), cardiac resynchronization therapy (CRT), and cardiac transplantation for end-stage disease [2,3,4]. None of these therapies are efficacious in arresting the loss of cardiomyocyte function and development of fibrosis in a failing heart, and the therapeutic option of cardiac transplantation remains unavailable to many due to the large gap between available donors and eligible recipients, further complicated by the need of long-term immunosuppression needed after a transplant
Evidence has emerged that suggests the possibility of regeneration of myocardial tissue using cardiac stem cells, based upon which numerous clinical trials are probing the use of stem cells from multiple origins as a therapeutic alternative in HF [5]
Summary
Despite the recent advances in medical therapy, Heart Failure (HF) remains a significant cause of mortality and morbidity worldwide. Conducted on patients with ischemic heart failure, findings from the C-CURE trial published in 2013 include improvement of LVEF from 27.5 ± 1.0% to 34.5 ± 1.1% in the test group that received MSC in addition to drug therapy (standard care) as compared to the control group that received standard care alone (from 27.8 ± 2.0% to 28.0 ± 1.8%), which was statistically significant (p
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