Ryanodine receptor stabilization therapy suppresses Ca2+- based arrhythmias in a novel model of metabolic HFpEF

Journal article

Heart Failure with preserved ejection fraction (HFpEF) has a high rate of sudden cardiac death (SCD) and empirical treatment is ineffective. We developed a novel preclinical model of metabolic HFpEF that presents with stress-induced ventricular tachycardia (VT). Mechanistically, we discovered arrhythmogenic changes in intracellular Ca²⁺ handling distinct from the changes pathognomonic for heart failure with reduced ejection fraction. We further show that dantrolene, a stabilizer of the ryanodine receptor Ca²⁺ channel, attenuates HFpEF-associated arrhythmogenic Ca²⁺ handling in vitro and suppresses stress-induced VT in vivo. We propose ryanodine receptor stabilization as a mechanistic approach to mitigation of malignant VT in metabolic HFpEF.

Authors: Kaplan, AD; Boyman, L; Ward, CW; Lederer, WJ; Greiser, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Journal of Molecular and Cellular Cardiology
• Volume: 195
• Pages: 68-72
• Publication date: 2024-07-23
• Acceptance date: 2024-07-19
• DOI: 10.1016/j.yjmcc.2024.07.006
• EISSN: 1095-8584
• ISSN: 0022-2828
• Language: English
• Keywords: heart failure; arrhythmia; calcium handling; metabolic stress