Long-term effects of non-excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs

Objective: We previously showed that acute delivery of non-excitatory cardiac contractility modulation (CCM) electric signal during the absolute refractory period improved LV function in dogs with chronic heart failure (1117). In the present study we examined the long-term effects of CCM signal delivery on the progression of LV dysfunction and remodeling in dogs with chronic HE Methods: Chronic HF was produced in 12 dogs by multiple sequential intracoronary microembolizations. The CCM signal was delivered using a lead implanted in the distal anterior coronary vein. A right ventricular and a right atrial lead were implanted and used for timing of CCM signal delivery. In six dogs, CCM signals were delivered continuously for 6 h daily with an average amplitude of 3.3 V for 3 months. Six HF dogs did not have leads implanted and served as controls. Results: In control dogs, LV end-diastolic volume (EDV) and IV end-systolic volume (ESV) increased (64 +/- 5 ml vs. 75 +/- 6 ml, P = 0.003; 46 +/- 4 ml vs. 57 +/- 4 ml, P = 0.003; respectively), and ejection fraction (EF) decreased (28 +/- 1% vs. 23 +/- 1%, P = 0.001) over the course of 3 months of follow-up. In contrast, CCM-treated dogs showed a smaller increase in EDV (66 +/- 4 vs. 73 +/- 5 ml, P = 0.01), no change in ESV, and an increase in EF from 31 +/- 1 to 34 +/- 2% (P = 0.04) after 3 months of therapy. Conclusions: In dogs with HE long-term CCM therapy prevents progressive LV dysfunction and attenuates global LV remodeling. These findings provide compelling rationale for exploring the use of CCM for the treatment of patients with chronic HE (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.