The Journal of Heart and Lung Transplantation
Volume 29, Issue 5 , Pages 554-561, May 2010

Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart

  • Monique L. Ogletree, PhD

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • ,
  • Wendy E. Sweet, MS

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • ,
  • Cassandra Talerico, PhD

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • ,
  • Mary E. Klecka, BA

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • ,
  • James B. Young, MD

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio
    • ,
  • Nicholas G. Smedira, MD

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
    • ,
  • Randall C. Starling, MD, MPH

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • ,
  • Christine S. Moravec, PhD

      Affiliations

    • Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
    • Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
    • Corresponding Author InformationReprint requests: Christine S. Moravec, PhD, Department of Cardiovascular Medicine, NE61, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. Telephone: 216-445-9949. Fax: 216-445-9951

published online 04 January 2010.

Background

Intracellular Ca2+ handling is abnormal in human heart failure. Studies have demonstrated that left ventricular assist device (LVAD) support reverses phenotypic alterations, suggesting that, in select patients, LVAD support may be a bridge to recovery. Few studies have related support duration to phenotypic recovery. We hypothesized that reversal of impaired sarcoendoplasmic reticulum (SR) Ca2+ cycling following LVAD implantation is duration-dependent.

Methods

We used post-rest potentiation to assess SR function, and Western blot analysis to measure Ca2+-cycling proteins. Left ventricular tissue from 10 non-failing hearts, 8 failing hearts and 10 LVAD-supported hearts was analyzed. Support ranged from 7 to 334 days. The median duration, 115 days, divided patients into short- and long-term support groups.

Results

Post-rest potentiation (PRP) response recovered after short-term LVAD support to a level (116.8 ± 12.1%; n = 5) close to non-failing (123.4 ± 12.0%; n = 10) hearts, but recovery after long-term support (23.5 ± 7.0%; n = 5) remained closer to that of failing hearts (13.5 ± 5.6%). We found a similar pattern of normalization for SR Ca2+-ATPase protein and the phospholamban/SR Ca2+-ATPase ratio (non-failing: 0.66 ± 0.11; failing: 1.21 ± 0.23; short-duration LVAD: 0.68 ± 0.14; long-duration LVAD: 1.67 ± 0.30; correlation p < 0.001; r = 0.93). The ratio also tended to correlate with the PRP response after unloading (p = 0.05; r = −0.65).

Conclusions

SR Ca2+ handling improved during early LVAD support, but long-term support was associated with abnormal Ca2+ cycling. These findings cast doubt on strategies designed to wean patients after complete unloading with an LVAD.

Keywords: heart failure, heart-assist device, contractility, Ca2+, sarcoendoplasmic reticulum Ca2+ ATPase

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 Current affiliation for M.L.O: Department of Molecular Physiology and Biophysics, University of Houston, Houston, Texas.

PII: S1053-2498(09)00848-1

doi:10.1016/j.healun.2009.10.015

The Journal of Heart and Lung Transplantation
Volume 29, Issue 5 , Pages 554-561, May 2010

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