Finding reliable parameters to identify patients with heart failure (HF) that will
respond to cardiac resynchronization therapy (CRT) represents a major challenge. We
and others have observed post-translational modifications of Ryanodine Receptor (RyR)
in several tissues (including skeletal muscle and circulating lymphocytes) of patients
with advanced HF. We designed a prospective study to test the hypothesis that RyR1
glycation in circulating lymphocytes could predict CRT responsiveness in patients
with non-ischemic HF. We enrolled 94 patients who underwent CRT and 30 individuals
without HF, examining RyR1 glycation in peripheral lymphocytes at enrollment and after
1 year. We found that baseline RyR1 glycation independently predicts CRT response
at 1 year after adjusting for age, diabetes, QRS duration and morphology, echocardiographic
dyssynchrony, and hypertension. Moreover, RyR1 glycation in circulating lymphocytes
significantly correlated with pathologic intracellular calcium leak. Taken together,
our data show for the first time that RyR1 glycation in circulating lymphocytes represents
a novel biomarker to predict CRT responsiveness.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of Heart and Lung TransplantationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance.Eur Heart J. 2020; 41: 3813-3823
- Septal flash: at the heart of cardiac dyssynchrony.Trends Cardiovasc Med. 2020; 30: 115-122
- Evaluation, management, and outcomes of patients poorly responsive to cardiac resynchronization device therapy.J Am Coll Cardiol. 2019; 74: 2588-2603
- Ryanodine receptor calcium leak in circulating B-lymphocytes as a biomarker in heart failure.Circulation. 2018; 138: 1144-1154
- Ryanodine receptor glycation favors mitochondrial damage in the senescent heart.Circulation. 2019; 139: 949-964
- Calcium release channel RyR2 regulates insulin release and glucose homeostasis.J Clin Invest. 2015; 125: 1968-1978
- Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure.Cell Commun Signal. 2017; 15: 47
- Characteristics of responders to cardiac resynchronization therapy: the impact of echocardiographic left ventricular volume.Clin Cardiol. 2012; 35: 777-780
- Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3beta.J Clin Invest. 2014; 124: 129-138
- Advances in the understanding of excitation-contraction coupling: the pulsing quest for drugs against heart failure and arrhythmias.Eur Heart J Cardiovasc Pharmacother. 2021; 7: e91-e93
Article info
Publication history
Published online: December 26, 2021
Identification
Copyright
© 2021 International Society for Heart and Lung Transplantation. All rights reserved.
