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Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na–K-ATPase inhibition: a new promising treatment for acute heart failure syndromes?

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Abstract

Acute heart failure syndromes (AHFS) are associated with the rapid onset of heart failure (HF) signs and symptoms. Hospitalizations for AHFS continue to rise and are associated with significant mortality and morbidity. Several pharmacological agents are currently approved for the treatment of AHFS, but their use is associated with an increase in short-term mortality. There is a need for new agents that can be given in the acute setting with increased efficacy and safety. Istaroxime is a unique agent with both inotropic and lusitropic properties which is currently being studied for the treatment of AHFS. Istaroxime inhibits the sodium–potassium adenosine triphosphatase (ATPase) and stimulates the sarcoplasmic reticulum calcium ATPase isoform 2 (SERCA-2) thereby improving contractility and diastolic relaxation. Early data from human studies reveal that istaroxime decreases pulmonary capillary wedge pressure (PCWP) and possibly improves diastolic function without causing a significant change in heart rate (HR), blood pressure, ischemic or arrhythmic events. Most commonly reported side effects were related to gastrointestinal intolerance and were dose related. In conclusion, istaroxime is a novel agent being investigated for the treatment of AHFS whose mechanism of action and cellular targets make it a promising therapy. Further studies with longer infusion times in patients with hypotension are required to confirm its efficacy and safety.

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Acknowledgments

Dr. Gheorghiade reports receiving research grants from the National Institutes of Health, Otsuka, Sigma-Tau, Merck, and Scios Inc.; being a consultant for Debiopharm, Errekappa Terapeutici, GlaxoSmithKline, Protein Design Laboratories, Medtronic, and Sigma-Tau; and receiving honoraria from Abbott, AstraZeneca, GlaxoSmithKline, Medtronic, Otsuka, Protein Design Laboratories, Scios Inc., and Sigma-Tau. Dr. Metra has occasionally received honoraria and reimbursement for travel expenses from Actelion, Corthera, Merck, NovaCardia, and Servier. Dr. Filippatos reports receiving research grants from the American Heart Association, University of Athens, Otsuka, Medtronic, Sigma-Tau, Roche Diagnostics, Biosite, Brahms. Dr. Sabbah reports receiving research grants and being a consultant to Sigma-Tau. Dr. Porchet is the Vice President Medical Affairs of Debiopharm S.A. Dr. Valentini is an employee of Sigma-Tau. Dr. Blair reports being a consultant for Debiopharm S.A. Dr’s. Khan and Harinstein have nothing to disclose. Mark Vogel has nothing to disclose.

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Authors and Affiliations

  1. Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

    Hashim Khan, John E. A. Blair, Mark Vogel & Matthew E. Harinstein

  2. Department of Cardiology, University of Brescia, Brescia, Italy

    Marco Metra

  3. University Hospital Attikon, Athens, Greece

    Gerasimos S. Filippatos

  4. Henry Ford Hospital, Detroit, MI, USA

    Hani N. Sabbah

  5. Debiopharm S.A., Lausanne, Switzerland

    Herve Porchet

  6. Sigma tau ifr, SpA, Rome, Italy

    Giovanni Valentini

  7. Division of Cardiology, Northwestern University, Feinberg School of Medicine, 676 North Saint Clair, Suite 600, Chicago, IL, 60611, USA

    Mihai Gheorghiade

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  1. Hashim Khan
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  2. Marco Metra
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  3. John E. A. Blair
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  7. Hani N. Sabbah
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  10. Mihai Gheorghiade
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Correspondence to Mihai Gheorghiade.

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Khan, H., Metra, M., Blair, J.E.A. et al. Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na–K-ATPase inhibition: a new promising treatment for acute heart failure syndromes?. Heart Fail Rev 14, 277–287 (2009). https://doi.org/10.1007/s10741-009-9136-z

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  • DOI: https://doi.org/10.1007/s10741-009-9136-z

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