Therapy With Cardiac Contractility Modulation Electrical Signals Improves Left Ventricular Function and Remodeling in Dogs With Chronic Heart Failure

ObjectivesThis study examined the effects of long-term delivery of cardiac contractility modulation (CCM) electric signals on left ventricular (LV) function and global, cellular, and molecular remodeling in dogs with chronic heart failure (HF).BackgroundAcute studies in dogs with experimentally induced HF showed that CCM signals applied to the failing myocardium during the absolute refractory period improved LV function without increasing myocardial oxygen consumption.MethodsIn one study, dogs with intracoronary microembolization-induced HF were randomized to 3 months of active CCM monotherapy or to a sham-operated control group. In another study, 19 HF dogs were randomized to 3 months chronic monotherapy with extended release metoprolol succinate (MET-ER), MET-ER with CCM, or no therapy at all (control group).ResultsIn CCM-only treated dogs, LV ejection fraction (EF) increased (27 ± 1% vs. 33 ± 1%, p < 0.0001) compared with a decrease in sham-operated control animals (27 ± 1% vs. 23 ± 1%, p < 0.001). The increase in EF seen with CCM-treated dogs was accompanied by reduced LV volumes, improved myocardial structure, reversal of the maladaptive fetal gene program, and an improvement in sarcoplasmic reticulum calcium cycling proteins. Dogs treated with a combination of MET-ER and CCM showed a greater increase in LV EF and a greater reversal of LV global, structural, and biochemical remodeling compared with dogs treated with MET-ER alone.ConclusionsIn dogs with HF, long-term CCM therapy improves LV systolic function. The improvements are additive to those seen with beta-blockers. These findings are further strengthened by the concomitant benefits of CCM therapy on LV global, cellular, and biochemical remodeling.