Cardiac Resynchronization Therapy and Bone Marrow Cell Transplantation in Patients with Ischemic Heart Failure and Electromechanical Dyssynchrony: A Randomized Pilot Study

Abstract

Most studies have confirmed the beneficial effects of autologous bone marrow mononuclear cell (BMMC) transplantation on angina, myocardial perfusion, regional wall motion, and LV ejection fraction (LVEF). Cardiac resynchronization therapy (CRT) has also shown a beneficial effect in patients with heart failure (HF) and electrical/mechanical dyssynchrony. However, the relative contribution of BMMC and CRT in patients with ischemic HF and electromechanical dyssynchrony has never been investigated. The aim of this study was to evaluate the benefit of combining BMMC transplantation with CRT in patients with severe ischemic HF, left bundle branch block (LBBB), and mechanical dyssynchrony. Patients with ischemic HF, LVEF < 35%, LBBB, and mechanical dyssynchrony underwent intramyocardial transplantation of BMMC and CRTD system implantation. This randomized, single-blind, crossover study compared clinical and echocardiographic parameters during two follow-up periods: 6 months of active CRT (BMMC + CRTact) and 6 months of inactive CRT (BMMC + CRTinact). Physical performance was assessed by means of a 6-min walking test. Myocardial perfusion was evaluated by SPECT. Quality of Life (QoL) was assessed through the Minnesota Living with HF Questionnaire (MLwHFQ). Twenty-six patients (64 ± 7 years) were enrolled in the study. The distance covered by the patients during the 6-min walking test significantly increased in the BMMC + CRTinact phase (BMMC therapy only) in comparison with the baseline (269 ± 68 vs 206 ± 51; p = 0.007) and in the BMMC + CRTact phase (BMMC therapy + CRT) in comparison with the BMMC + CRTinact (378 ± 59 vs 269 ± 68; p < 0.001). The summed rest and stress score (SPECT) decreased significantly in the BMMC + CRTact and BMMC + CRTinact phases in comparison with the baseline (p ≤ 0.03). Both phases showed equivalent myocardial perfusion in the segments into which BMMC had been injected. QoL score was significantly lower in the BMMC + CRTinact phase than at the baseline (44.1 ± 14 vs 64.8 ± 19; p < 0.001), and in the BMMC + CRTact phase than in the BMMC + CRTinact phase (26.4 ± 12 vs 44.1 ± 14; p = 0.004). BMMC and CRT seem to act independently on myocardial perfusion and electromechanical dyssynchrony, respectively. Combining these two complementary therapies can significantly improve LV performance in patients with severe HF and electromechanical dyssynchrony.

Induced pluripotent stem cell intervention rescues ventricular wall motion disparity, achieving biological cardiac resynchronization post‐infarction

“…Potential applications of stem cell‐based resynchronization include non‐responders to current optimal therapies, and prophylactic early intervention for high‐risk groups in heart failure. The concept of biological cell‐based resynchronization, as opposed to traditional device‐based resynchronization, is supported by recent clinical and preclinical evidence (Chang et al 2008; Herbots et al 2009; van Ramshorst et al 2009; Bonios et al 2011; Pokushalov et al 2011). Due to complexity in the regulation of myocardial mechanics, as well as to the study design focusing on prospective in vivo imaging, the relationship of injury, regeneration and resynchronization processes is yet to be fully delineated.…”

Cardiac Resynchronization Therapy and QRS Duration: Systematic Review, Meta-analysis, and Meta-regression

“…One study enrolled patients undergoing coronary artery bypass graft (CABG) surgery and randomized to CRT-P with CABG or CABG alone ( 26 ). Another study compared CRT-D plus bone marrow mononuclear cell transplantation (BMMC) to BMMC alone ( 27 ). Two trials had not been published in peer-reviewed journals, so data were extracted from online source ( 28 , 29 ).…”

“…In one of these trials, the decision to implant CRT-P or CRT-D was left to the discretion of the treating physician, and patients were randomized to CRT-ON or CRT-OFF groups while keeping a double dummy ( 4 ). Another trial enrolled patients undergoing BMMC, which cannot be classified as a "conventional" medical treatment ( 27 ). Meta-analysis showed that CRT was associated with a significant survival benefit when compared to medical treatment (OR, 0.64; 95% CI, 0.53-0.78; P <0.001) but not when compared to ICD (OR, 0.98; 95% CI, 0.77-1.26; P =0.901, P for interaction=0.024).…”

Advanced Strategies for End-Stage Heart Failure: Combining Regenerative Approaches with LVAD, a New Horizon?

“…The unloaded ventricle provides a less hostile milieu and thereby a potentially more appropriate platform for different regenerative therapies. Along the same lines, the combined approach of biventricular pacing and BMMNCs in ischemic HF indicated a significant and clinically relevant improvement in cardiac function in comparison with BMMNCs alone, while CRT showed no impact on perfusion ( 97 ). The rationale for this approach is that electrical stimulation might promote cell differentiation.…”