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Cardiac Contractility Modulation With the Impulse Dynamics Signal: Studies in Dogs With Chronic Heart Failure

Heart Failure Reviews volume 6, pages 45–53 (2001)Cite this article

Abstract

The intravenous use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure is limited by pro-arrhythmic and positive chronotropic effects. Chronic use of these agents, while eliciting an improvement in the quality of life of patients with advanced heart failure, has been abandoned because of marked increase in mortality when compared to placebo. Nevertheless, patients with advanced heart failure can benefit from long-term positive inotropic support if the therapy can be delivered ‘on demand’ and in a manner that is both safe and effective. In this review, we will examine the use of a novel, non-stimulatory electrical signal that can acutely modulate left ventricular (LV) contractility in dogs with chronic heart failure in such a way as to elicit a positive inotropic support. Cardiac contractility modulation (CCM) with the Impulse Dynamic™ signal was examined in dogs with chronic heart failure produced by intracoronary microembolizations. Delivery of the CCM signal from a lead placed in the great coronary vein for periods up to 10 minutes resulted in significant improvements in cardiac output, LV peak+dP/dt, LV fractional area of shortening and LV ejection fraction measured angiographically. Discontinuation of the signal resulted in a return of all functional parameters to baseline values. In cardiomyocytes isolated from dogs with chronic heart failure, application of the CCM signal resulted in improved shortening, rate of change of shortening and rate of change of relengthening suggesting that CCM application is associated with intrinsic improvement of cardiomyocyte function. The improvement in isolated cardiomyocyte function after application of the CCM signal was accompanied by an increase in the peak and integral of the Ca2+ transient suggesting modulation of calcium cycling by CCM application. In a limited number of normal dogs, intermittent chronic delivery of the CCM signal for up to 7 days showed chronic maintenance of LV functional improvement. In conclusion, pre-clinical results to date with the Impulse Dynamics CCM signal indicate that this non-pharmacologic therapeutic modality can provide short-term positive inotropic support to the failing heart and as such, may be a useful adjunct in the treatment of advanced heart failure. Additional, long-term studies in dogs with heart failure are needed to establish the safety and efficacy of this therapeutic modality for the chronic treatment of this disease syndrome.

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Affiliations

  1. Department of Medicine & Division of Cardiovascular Medicine, Henry Ford Heart & Vascular Institute, Detroit, Michigan, U.S.A

    Hani N. Sabbah PhD, Omar Nass MD, Victor G. Sharov MD, PhD, Victor Maltsev PhD, Albertas I. Undrovinas PhD & Sidney Goldstein MD

  2. Impulse Dynamics, Tirat Hacarmel, Israel

    Walid Haddad PhD, Yuval Mika DSc, Ricardo Aviv PhD, Bella Felzen PhD, Nissim Darvish MD & Shlomo A. Ben-Haim MD, PhD

  3. Department of Physiology and Biophysics, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel

    Shlomo A. Ben-Haim MD, PhD

Authors
  1. Hani N. Sabbah PhD
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  2. Walid Haddad PhD
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  3. Yuval Mika DSc
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  4. Omar Nass MD
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  5. Ricardo Aviv PhD
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  6. Victor G. Sharov MD, PhD
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  7. Victor Maltsev PhD
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  8. Bella Felzen PhD
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  9. Albertas I. Undrovinas PhD
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  10. Sidney Goldstein MD
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  11. Nissim Darvish MD
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  12. Shlomo A. Ben-Haim MD, PhD
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Sabbah, H.N., Haddad, W., Mika, Y. et al. Cardiac Contractility Modulation With the Impulse Dynamics Signal: Studies in Dogs With Chronic Heart Failure. Heart Fail Rev 6, 45–53 (2001). https://doi.org/10.1023/A:1009855208097

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  • DOI: https://doi.org/10.1023/A:1009855208097

  • congestive heart failure
  • contractility
  • ventricular function
  • animal models