Bone marrow‐derived mesenchymal stromal cell treatment in patients with ischaemic heart failure: final 4‐year follow‐up of the MSC‐HF trial

Abstract

AimsThe study assessed 4-year outcomes of intramyocardial injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with ischaemic heart failure.The MSC-HF trial was a randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to intramyocardial injections of MSCs or placebo. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography. Sixty patients aged 30-80 years with ischaemic heart failure, New York Heart Association class II-III, left ventricular ejection fraction (LVEF) <45% and no further treatment options were randomized. Patients were followed clinically for 12 months and in addition 4-year data of hospitalizations and survival were retrieved. After 12 months, LVESV was significantly reduced in the MSC group and not in the placebo group, with difference between groups of 17.0 ± 16.2 mL (95% confidence interval 8.3-25.7, P = 0.0002). There were also significant improvements in LVEF of 6.2% (P < 0.0001), stroke volume of 16.1 mL (P < 0.0001) and myocardial mass (P = 0.009) between groups. A significant dose-response effect was also observed. Moreover, a significant reduction in the amount of scar tissue and quality of life score in the MSC group but not in the placebo group was observed. After 4 years, there were significantly fewer hospitalizations for angina in the MSC group and otherwise no differences in hospitalizations or survival. No side effects were identified.

Time to end the war on cell therapy

“…Overall, the 12‐month results confirm and extend those reported previously at 6 months . The present paper is important because it indicates that, in patients with ischaemic HF, a single injection of autologous MSCs produces an improvement in left ventricular function and structure that is sustained for at least 12 months, and may be associated with clinical benefits for up to 4 years. The increase in LVEF (+6.2 units relative to control) was comparable to that effected by commonly used interventions such as early reperfusion in ST‐elevation myocardial infarction or cardiac resynchronization therapy.…”

“…In this issue of the Journal, Mathiasen and colleagues report the final results of MSC‐HF, a randomized, double‐blind, placebo‐controlled, Phase II study that evaluated transendocardial injection of autologous bone marrow (BM)‐derived mesenchymal stromal cells (MSCs) in 60 patients with ischaemic heart failure (HF) . At 12 months after MSC administration, there was a significant improvement in the primary endpoint [change in left ventricular end‐systolic volume (LVESV)] relative to placebo (−17 mL; P < 0.0002).…”

“…ixCELL‐DCM (a Phase IIb multicentre trial in 109 patients at 31 sites) demonstrated a 37% reduction in the primary endpoint (death, cardiac hospitalization, acute decompensated HF) . MSC‐HF (discussed above) showed an improvement in the primary endpoint (left ventricular function) in 60 patients . These studies are definitely not ‘futile’.…”

May 2020 at a glance: ischaemic heart failure and sex‐related differences

“…Treatment of ischaemic HF with mesenchymal stem cells is an area of active research 11 . Mathiesen et al 11 .…”

“…Treatment of ischaemic HF with mesenchymal stem cells is an area of active research 11 . Mathiesen et al 11 . reported the long‐term results of the Autologous Mesenchymal Stromal Cell Therapy in Heart Failure (MCS‐HF) trial, a 2:1 randomized double‐blind trial comparing intramyocardial injections of autologous mesenchymal stromal cells (MSCs) vs. placebo in patients with ischaemic HF.…”