Abstract
Cardiac contractility modulation (CCM) is the application of nonexcitatory electrical signals to the myocardium, during the absolute refractory period of the action potential, to elicit a positive inotropic effect without increasing myocardial oxygen consumption. These effects are independent of QRS duration; consequently, CCM device therapy might benefit symptomatic patients with reduced left ventricular ejection fraction who are not candidates for cardiac resynchronization therapy. Preclinical studies have demonstrated a rapid positive inotropic effect of CCM, which seems to be mediated by modulation of cardiomyocyte Ca2+ fluxes and alterations in the phosphorylation of cardiac phospholamban. In vivo translational and clinical studies that utilized double biphasic voltage pulses to the right ventricular aspect of the interventricular septum have demonstrated positive global effects on cardiac reverse remodelling and contractility. Long-term application of CCM seems to improve patients' exercise tolerance and quality of life. These benefits are apparently accomplished with an acceptable safety profile; however, to date, no data have demonstrated reductions in hospitalizations for heart failure or mortality. CCM is currently available in Europe and ongoing studies are attempting to identify the ideal target population and accumulate additional outcome data.
Key Points
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Cardiac contractility modulation (CCM) is the application of nonexcitatory electrical signals to the myocardium, during the absolute refractory period of the action potential, to augment contraction without increasing oxygen consumption
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Preclinical studies evolved from using high-amplitude monophasic current pulses to using double-biphasic voltage pulses; the latter have been used in all clinical trials
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The mechanisms underpinning the effects of CCM are still unclear but might be partly mediated by alterations in myocyte Ca2+ transients and cardiac phospholamban phosphorylation
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In patients with NYHA class III–IV heart failure, CCM improves reverse remodelling and contractility, independent of QRS duration; these benefits are additive to those of cardiac resynchronization therapy (CRT)
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CCM improves peak oxygen consumption and quality of life, and these benefits are of a comparable magnitude to those achieved using cardiac resynchronization therapy in patients with prolonged QRS duration
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Ongoing studies of CCM are generating clinical outcome data and aim to identify the ideal target population for this therapy
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Change history
04 February 2014
In the version of this article originally published, the address for Alexander R. Lyon was incorrectly stated. The address should have been: NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. This error has been corrected in the HTML and PDF versions of the article.
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Lyon, A., Samara, M. & Feldman, D. Cardiac contractility modulation therapy in advanced systolic heart failure. Nat Rev Cardiol 10, 584–598 (2013). https://doi.org/10.1038/nrcardio.2013.114
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DOI: https://doi.org/10.1038/nrcardio.2013.114
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