Cardiac Resynchronization and Circulating Markers of Sarcoplasmic Reticulum Calcium Handling and Sudden Death Risk

Ning Jiang, Anyu Zhou, Hafiz Imran, Guangbin Shi, Bahaa Kaseer, Vincent Siu, Antony F. Chu, David M. Donaldson, Malcolm M. Kirk, Binu B. Philips, Samuel C. Dudley

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Cardiac resynchronization therapy (CRT) can improve heart function and decrease arrhythmic events. We tested whether CRT altered circulating markers of calcium handling and sudden death risk. Circulating cardiac sodium channel messenger RNA (mRNA) splicing variants indicate arrhythmic risk, and a reduction in sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) is thought to diminish contractility in heart failure. CRT was associated with a decreased proportion of circulating, nonfunctional sodium channels and improved SERCA2a mRNA expression. Patients without CRT did not have improvement in the biomarkers. These changes might explain the lower arrhythmic risk and improved contractility associated with CRT.

Original languageEnglish (US)
Pages (from-to)1079-1083
Number of pages5
JournalJACC: Clinical Electrophysiology
Issue number9
StatePublished - Sep 2021

Bibliographical note

Funding Information:
Dr Dudley is the inventor on the following patent applications: SCN5A Splice Variants for Use in Methods Relating to Sudden Cardiac Death and Need for Implanted Cardiac Defibrillators, PCT/US2012/20564; and SCN5A Splicing Factors and Splice Variants for Use in Diagnostic and Prognostic Methods, 13/291,826. Supported by National Institutes of Health grants R01 HL104025 and HL106592. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 American College of Cardiology Foundation


  • biomarker
  • calcium
  • implantable cardioverter-defibrillator
  • ion channels
  • sodium channel


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