Calcium and Heart Failure: How Did We Get Here and Where Are We Going?

Int J Mol Sci. 2021 Jul 9;22(14):7392. doi: 10.3390/ijms22147392.


The occurrence and prevalence of heart failure remain high in the United States as well as globally. One person dies every 30 s from heart disease. Recognizing the importance of heart failure, clinicians and scientists have sought better therapeutic strategies and even cures for end-stage heart failure. This exploration has resulted in many failed clinical trials testing novel classes of pharmaceutical drugs and even gene therapy. As a result, along the way, there have been paradigm shifts toward and away from differing therapeutic approaches. The continued prevalence of death from heart failure, however, clearly demonstrates that the heart is not simply a pump and instead forces us to consider the complexity of simplicity in the pathophysiology of heart failure and reinforces the need to discover new therapeutic approaches.

Keywords: beta blocker; calcium transient; excitation–contraction coupling; heart failure; hypoxia; inotrope; myocardial contractility; myofilament; sarcoplasmic reticulum; sarcoplasmic reticulum Ca2+ ATPase.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adrenergic beta-1 Receptor Agonists / pharmacology
  • Adrenergic beta-1 Receptor Agonists / therapeutic use
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • Ca(2+) Mg(2+)-ATPase / metabolism*
  • Calcium / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cardiotonic Agents / pharmacology
  • Dobutamine / pharmacology
  • Dobutamine / therapeutic use
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Myocardial Contraction / physiology*
  • Sarcoplasmic Reticulum / metabolism*


  • Adrenergic beta-1 Receptor Agonists
  • Adrenergic beta-Antagonists
  • Antioxidants
  • Cardiotonic Agents
  • Dobutamine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Adenosine Triphosphatases
  • Ca(2+) Mg(2+)-ATPase
  • Calcium