Transendocardial CD34+ Cell Therapy Improves Local Mechanical Dyssynchrony in Patients With Nonischemic Dilated Cardiomyopathy

Abstract

We investigated the effects of cell therapy on local mechanical dyssynchrony (LMD) in patients with nonischemic dilated cardiomyopathy (NICM). We analyzed electromechanical data of 30 NICM patients undergoing CD34⁺ cell transplantation. All patients underwent bone marrow stimulation; CD34⁺ cells were collected by apheresis and injected transendocardially. At baseline and at 6 months after therapy, we performed electromechanical mapping and measured unipolar voltage (UV) and LMD at cell injection sites. LMD was defined as a temporal difference between global and segmental peak systolic displacement normalized to the average duration of the RR interval. Favorable clinical response was defined as increase in the left ventricular ejection fraction (LVEF) ≥5% between baseline and 6 months. Using paired electromechanical point-by-point analysis, we were able to identify 233 sites of CD34⁺ cell injections in 30 patients. We found no overall differences in local UV between baseline and 6 months (10.7 ± 4.1 mV vs 10.0 ± 3.6 mV, P = 0.42). In contrast, LMD decreased significantly (17 ± 17% at baseline vs 13 ± 12% at 6 months, P = 0.00007). Favorable clinical response at 6 months was found in 19 (63%) patients (group A), and 11 (37%) patients did not respond to cell therapy (group B). At baseline, the two groups did not differ in age, gender, LVEF, or N terminal-pro brain natriuretic peptide (NT-proBNP) levels. Similarly, we found no differences in baseline UV (9.5 ± 2.9 mV in group A vs 8.6 ± 2.4 mV in group B, P = 0.41) or LMD at cell injection sites (17 ± 19% vs 16 ± 14%, P = 0.64). In contrast, at 6 months, we found higher UV in group A (10.0 ± 3.1 mV vs 7.4 ± 1.9 mV in group B, P = 0.04). Furthermore, when compared with group B, patients in group A displayed a significantly lower LMD (11 ± 12% vs 16 ± 10%, P = 0.002). Thus, it appears that favorable clinical effects of cell therapy in NICM patients may be associated with a decrease of LMD at cell injection sites.

Keywords: dilated cardiomyopathy; mechanical dyssynchrony; stem cells.

Figure 1.

Flowchart of the study design.

Figure 2.

Local mechanical dyssynchrony measurement. The figure represents electromechanical tracings measured at a specific mapping point (lower panel), and their schematic representation (upper panel). Yellow line depicts global ventricular movement and black line (upper panels) or white line (bottom panels) depicts movement of a selected myocardial segment. In synchronous segmental movement (panel A), the two lines are synchronized. In panel B, the two lines are discordant, demonstrating a mechanical dyssynchrony of a given segment of the left ventricle.

Figure 3.

Changes in local mechanical dyssynchrony and unipolar voltage after cell therapy. Using paired electromechanical point-by point analysis, we found a significant decrease in LMD at cell injected sites between baseline and 6-month follow-up. However, we did not observe any significant changes in local UV. Data are presented as median (IQR). IQR: interquartile range; LMD: local mechanical dyssynchrony; UV: unipolar voltage.

Figure 4.

Changes in local mechanical dyssynchrony and unipolar voltage in clinical responders and nonresponders. At baseline, no differences were found comparing LMD or UV at cell injection sites between responders (group A) and nonresponders (group B). At 6 months, a significant decrease in LMD and a significant increase in UV were observed in responders, but not in nonresponders (panel A; data presented as mean ± SD). Panel B represents repeated-measures one-way ANOVA of LMD and UV at baseline and 6-month follow-up in group A and group B. ANOVA: analysis of variance; LMD: local mechanical dyssynchrony; UV: unipolar voltage.