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August 20, 2026Journal of the American College of Cardiology

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

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Key result

Cardiac contractility modulation increases LVEF by ~10% versus sham in dogs with chronic heart failure.

  • P<0.0001

Why the study?

Acute studies showed cardiac contractility modulation improved LV function without increasing oxygen consumption, but the effects of long-term delivery on LV function and remodeling remained to be examined.

Does cardiac contractility modulation improve left ventricular function and remodeling in dogs with chronic heart failure?

Population

Dogs with intracoronary microembolization-induced chronic HF (including 19 dogs in a second study)

Comparison

CCM monotherapy vs sham, and MET-ER plus CCM vs MET-ER monotherapy vs no therapy

Design

Randomized controlled animal study

Follow-up

3 months

Authors

MIMakoto ImaiSRSharad RastogiRGRamesh C. Gupta

Discussion

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Overview

CCM improves LV function in canine HF; leaves open translation to patients pending clinical trials.

Key Points

  • To evaluate the long-term effects of cardiac contractility modulation (CCM) electrical signals on left ventricular systolic function and multi-level structural and molecular remodeling in chronic heart failure.
  • Canine models of intracoronary microembolization-induced heart failure were randomized to 3 months of active CCM monotherapy or sham-operated control.
  • A separate cohort of 19 heart failure dogs was randomized to 3 months of extended-release metoprolol succinate (MET-ER), MET-ER combined with CCM, or an untreated control group.
  • CCM monotherapy significantly increased left ventricular ejection fraction from 27 ± 1% to 33 ± 1% (p < 0.0001), while ejection fraction decreased in sham controls from 27 ± 1% to 23 ± 1% (p < 0.001).
  • CCM delivery led to reduced left ventricular volumes, improved myocardial structure, reversal of the maladaptive fetal gene program, and restoration of sarcoplasmic reticulum calcium cycling proteins.
  • Combination therapy with MET-ER and CCM produced greater increases in ejection fraction and more pronounced reversal of structural and biochemical remodeling than MET-ER alone.

Study Design

Type

RCT

Randomization

Randomized

Structured PICO

Does cardiac contractility modulation improve left ventricular function and remodeling in dogs with chronic heart failure?

P
Population
Dogs with intracoronary microembolization-induced chronic heart failure followed for 3 months.
I
Intervention
Cardiac contractility modulation (CCM) electric signals delivered for 3 months, either as monotherapy or combined with extended release metoprolol succinate (MET-ER)
C
Comparator
Sham-operated control, no therapy, or MET-ER alone
O
Outcome
Left ventricular (LV) function (ejection fraction) and global, cellular, and molecular remodelingsurrogate

Main Result

Absolute Event Rate: 33% vs 23%

p-value: p=< 0.0001

Long-term cardiac contractility modulation therapy improves LV systolic function and reverses remodeling in a canine model of heart failure, with additive benefits when combined with beta-blockers.

Cite This Study

Imai et al. (2007) conducted an RCT in Chronic heart failure (HF). Cardiac contractility modulation (CCM) vs. Sham-operated control or no therapy was evaluated on Left ventricular ejection fraction (EF) (p=< 0.0001). In dogs with chronic heart failure, 3 months of cardiac contractility modulation increased left ventricular ejection fraction to 33% compared to a decrease to 23% in sham-operated controls.

synapsesocial.com/papers/6a871aec0d8e255da0bc2985https://doi.org/10.1016/j.jacc.2006.10.082
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Long-Term Effects of Non-Excitatory Cardiac Contractility Modulation Electric Signals on the Progression of Heart Failure in Dogs2004 · 40 citations
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