Intramyocardial Bone Marrow–Derived Mononuclear Cell Injection for Chronic Myocardial Ischemia

Abstract

Background— The present substudy of a recently published randomized trial aimed to investigate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia. Methods and Results— In a total of 50 patients, diastolic function was evaluated before and 3 months after bone marrow cell injection using standard echocardiography and strain analysis. In addition, MRI-derived transmitral flow measurements were obtained in a subset of 36 patients. Left ventricular ejection fraction increased from 50±5% to 54±7% in the bone marrow cell group, which was a significant improvement as compared with the placebo group (52±5% versus 51±7%, P =0.001). Filling pressure estimate E/E′ ratio improved from 14±5 at baseline to 12±4 at 3 months in the bone marrow cell group, whereas no improvement was observed in the placebo group (13±4 versus 13±5). The improvement in E/E′ ratio was significantly larger in the bone marrow cell group ( P =0.008). Furthermore, the E/A peak flow ratio as assessed by MRI showed a significant increase in the bone marrow cell group as compared with the placebo group (+0.16±0.25 versus −0.04±0.21, P =0.01), which was mainly related to an increase in the early (E) peak flow rate in the bone marrow cell group (from 407±96 mL/s to 468±110 mL/s, P =0.009 as compared with the placebo group). Conclusions— The current study demonstrates that intramyocardial bone marrow cell injection is associated with a beneficial effect on myocardial relaxation and filling pressures in patients with chronic myocardial ischemia. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR400/ISRCTN58194927.

Deformation imaging to assess global and regional effects of cardiac regenerative therapy in ischaemic heart disease: A systematic review

“…Four papers (Beitnes et al, ; Bhatti et al, ; Lebrun et al, ; Nasseri et al, ) found no significant effect of cell therapy on either regional strain (range −0.2% to 2.6% for the intervention groups compared with 3.0–3.3% for the control groups), global strain (range 2.1–2.5% vs. 0.4–2.4%) or LVEF (range 1.8–2.5% vs. −0.1 to 1.0%), implying no statistically significant beneficial effect of cell therapy on cardiac function. On the contrary, four papers (Plewka et al, ; Qi et al, ; Van Ramshorst et al, ; Van Ramshorst et al, ) show a positive effect of cardiac stem cell therapy on both regional (range 1–3.2% for the intervention groups vs. 0–2.3% for the control groups) and global (range 0.8–5.5% vs. −1.2% to 2.3%) deformation outcomes, as well as LVEF measurement (range 4–13% vs. −3% to 6.7%). Qi et al () showed a beneficial effect of cell therapy on LVEF but only found global longitudinal strain to show a significant positive effect of cell therapy, as opposed to global circumferential strain and regional longitudinal and circumferential strain.…”

“…Qi et al () showed a beneficial effect of cell therapy on LVEF but only found global longitudinal strain to show a significant positive effect of cell therapy, as opposed to global circumferential strain and regional longitudinal and circumferential strain. Three papers (Plewka et al, ; Van Ramshorst et al, ; Van Ramshorst et al, ) showed regional and global longitudinal strain as a positive outcome measurement of cardiac cell therapy. A total of six papers (Heldman et al, ; Herbots et al, ; Karatasakis et al, ; Malliaras et al, ; Nasseri et al, ; Williams et al, ) found a significant positive effect of cell therapy on regional longitudinal (range 3.7–7.5% for cell treatment groups, no within‐group analyses of control groups supplied) or circumferential (range 2.9–4.9% vs. 0.03% in control patients) strain, whereas an effect on LVEF (range 2.5–5.4% vs. −5.0% to 5.8%) was not detected ( n = 5) or was not mentioned ( n = 1).…”

Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis

“…From these, 69 citations were excluded as they did not fully meet the inclusion criteria (Figure 1). The remaining 11 full text articles and 19 conference abstracts contributed to nine independent trials [12]–[26] included in this systematic review. The characteristics of the included studies are shown in Table S1.…”

Bone Marrow Therapies for Chronic Heart Disease

“…Recently, van Ramshorst et al reported a randomized double‐blinde clinical trial of intramyocardial injection of bone marrow mononuclear cells in subjects with chronic myocardial ischemia refractory to medical treatment. There was approximately a 3% absolute increase in left ventricular ejection fraction (LVEF) after 3 months, improved MRI‐derived and tissue Doppler imaging‐derived parameters of diastolic function, and a substantial increase in quality‐of‐life score . In another study with chronic heart failure subjects received intracoronary bone marrow mononuclear cells after treatment of the heart with low‐energy ultrasound shock waves.…”