Intramyocardial bone marrow cell injection does not lead to functional improvement in patients with chronic ischaemic heart failure without considerable ischaemia.

I Mann,P Dibbets-Schneider,S L Beeres,R Wolterbeek,J Van Ramshorst,H J Lamb,M J Schalij,W E Fibbe,S A J Chamuleau,D E Atsma,L F De Geus-Oei,S F Rodrigo,P A Doevendans,J J Bax,J J Zwaginga,S Koudstaal,C C S Tseng,K Westinga

doi:10.1007/s12471-018-1213-2

Abstract

BackgroundIt has been suggested that bone marrow cell injection may have beneficial effects in patients with chronic ischaemic heart disease. However, previous trials have led to discrepant results of cell-based therapy in patients with chronic heart failure. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia.Methods and resultsThis multicentre, randomised, placebo-controlled trial included 39 patients with no-option chronic ischaemic heart failure with a follow-up of 12 months. A total of 19 patients were randomised to autologous intramyocardial bone marrow cell injection (cell group) and 20 patients received a placebo injection (placebo group). The primary endpoint was the group difference in change of left ventricular ejection fraction, as determined by single-photon emission tomography. On follow-up at 3 and 12 months, change of left ventricular ejection fraction in the cell group was comparable with change in the placebo group (P = 0.47 and P = 0.08, respectively). Also secondary endpoints, including left ventricle volumes, myocardial perfusion, functional and clinical parameters did not significantly change in the cell group as compared to placebo. Neither improvement was demonstrated in a subgroup of patients with stress-inducible ischaemia (P = 0.54 at 3‑month and P = 0.15 at 12-month follow-up).ConclusionIntramyocardial bone marrow cell injection does not improve cardiac function, nor functional and clinical parameters in patients with severe chronic ischaemic heart failure with limited stress-inducible ischaemia.Clinical Trial Registration: NTR2516Electronic supplementary materialThe online version of this article (10.1007/s12471-018-1213-2) contains supplementary material, which is available to authorized users.

Highlights

In patients with ischaemic heart disease, myocardial damage can lead to remodelling of the left ventricle and progress towards end-stage heart failure (HF) [1]
The first clinical trials with bone marrow cells were performed in patients after an acute myocardial infarction [7, 8] and showed contradictory results with regard to beneficial effects
There have been no clinical studies that evaluated whether the presence or absence of stress-inducible ischaemia influences the outcome of bone marrow cell treatment in patients with ischaemic HF

Summary

Introduction

In patients with ischaemic heart disease, myocardial damage can lead to remodelling of the left ventricle and progress towards end-stage heart failure (HF) [1]. Bone marrow cells have been evaluated in patients with chronic ischaemia and refractory angina pectoris with optimised therapy and without longterm treatment options (‘no-option’) [9,10,11] These latter trials demonstrated that intramyocardial injections with bone marrow cells are safe and result in improvement of cardiac function, myocardial perfusion and anginal symptoms [9,10,11]. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia. Methods and results This multicentre, randomised, placebo-controlled trial included 39 patients with nooption chronic ischaemic heart failure with a followup of 12 months. On follow-up at 3 and 12 months, change of left ventricular ejection frac-

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