Therapy with cardiac contractility modulation electrical signals improves left ventricular function and remodeling in dogs with chronic heart failure.
OBJECTIVE
This 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).


BACKGROUND
Acute 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.


METHODS
In 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).


RESULTS
In 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.


CONCLUSIONS
In 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.
Imai
Makoto
M
Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA.
Rastogi
Sharad
S
Gupta
Ramesh C
RC
Mishra
Sudhish
S
Sharov
Victor G
VG
Stanley
William C
WC
Mika
Yuval
Y
Rousso
Benny
B
Burkhoff
Daniel
D
Ben-Haim
Shlomo
S
Sabbah
Hani N
HN
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017147:Defibrillators, Implantable; D004195:Disease Models, Animal; D004285:Dogs; D004554:Electric Countershock / Q000379:methods*; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008790:Metoprolol / Q000031:analogs & derivatives / Q000494:pharmacology; D009200:Myocardial Contraction; D011897:Random Allocation; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D020257:Ventricular Remodeling
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol