Calcium Cycling in Heart Failure: The Arrhythmia Connection


  • This work was supported by National Institutes of Health Grant HL-46929 to Dr. Pogwizd and Grants HL-30077 and HL-64724 to Dr. Bers.

Address for correspondence: Steven M. Pogwizd, M.D., Section of Cardiology, University of Illinois at Chicago, 840 S. Wood Street, M/C 787, Chicago, IL 60612. Fax: 312-413-1616; E-mail:


Calcium Cycling in Heart Failure. Ventricular tachycardia in nonischemic heart failure (HF) arises from a nonreentrant mechanism most likely due to delayed afterdepolarizations from activation of a transient inward current (Iti). We present data and a paradigm in which an up-regulated Na/Ca exchanger, residual-adrenergic responsiveness, and decreased inward rectifying K current (IK1) in HF all conspire to markedly increase the propensity for triggered arrhythmias. The up-regulated Na/Ca exchanger plays an additional critical role in unloading the sarcoplasmic reticulum of Ca, thereby causing the mechanical dysfunction. It is imperative that therapeutic approaches for ventricular tachycardia in HF take into consideration cellular Ca handling and excitation-contractile coupling, and their alteration in the failing heart.