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Updated: Feb 3, 2026
Cardiac Response to β-Adrenergic Stimulation Determined by Pressure-Volume Loop Analysis
Published on: May 19, 2021
Arrhythmogenic Mechanisms in Heart Failure: Linking β-Adrenergic Stimulation, Stretch, and Calcium
Daniel M Johnson1, Gudrun Antoons2
1Department of Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
Insights
This review explores how beta-adrenergic stimulation and mechanical load in heart failure (HF) disrupt calcium handling in heart cells. These disruptions increase the risk of arrhythmias, offering targets for new HF therapies.
Area of Science:
- Cardiology
- Molecular Biology
- Electrophysiology
Background:
- Heart failure (HF) involves increased sympathetic tone and mechanical load, contributing to cardiac dysfunction.
- These factors can lead to electrical instability in the heart, particularly through altered calcium (Ca2+) handling in cardiac myocytes.
- This review focuses on the interplay between these elements and their role in heart failure-associated arrhythmias.
Purpose of the Study:
- To provide a comprehensive overview of the connections between beta-adrenergic stimulation, mechanical load, and arrhythmogenesis in heart failure.
- To elucidate the mechanisms by which Ca2+ handling alterations contribute to electrical instability in HF.
- To identify common pathways for potential therapeutic interventions.
Main Methods:
- Review of existing literature on beta-adrenergic signaling, mechanical stress, and cardiac arrhythmias in heart failure.
- Analysis of the role of Ca2+ handling, afterdepolarizations, and ion channel function.
- Discussion of cellular remodeling and microdomain alterations in HF.
Main Results:
- Beta-adrenergic stimulation and mechanical load can induce afterdepolarizations, increasing arrhythmia risk.
- Alterations in Ca2+ handling, including ryanodine receptor sensitivity and stretch-activated channels, are implicated in HF-related arrhythmias.
- Remodeling in HF exacerbates these arrhythmogenic triggers.
Conclusions:
- The cross-talk between beta-adrenergic signaling, mechanical load, and Ca2+ dysregulation is a key driver of arrhythmias in heart failure.
- Understanding these mechanisms can guide the development of novel therapeutic strategies targeting common pathways.
- Interventions aimed at modulating Ca2+ handling or downstream signaling may mitigate HF-associated electrical instability.
Abstract:
Heart failure (HF) is associated with elevated sympathetic tone and mechanical load. Both systems activate signaling transduction pathways that increase cardiac output, but eventually become part of the disease process itself leading to further worsening of cardiac function. These alterations can adversely contribute to electrical instability, at least in part due to the modulation of Ca2+ handling at the level of the single cardiac myocyte. The major aim of this review is to provide a definitive overview of the links and cross talk between β-adrenergic stimulation, mechanical load, and arrhythmogenesis in the setting of HF. We will initially review the role of Ca2+ in the induction of both early and delayed afterdepolarizations, the role that β-adrenergic stimulation plays in the initiation of these and how the propensity for these may be altered in HF. We will then go onto reviewing the current data with regards to the link between mechanical load and afterdepolarizations, the associated mechano-sensitivity of the ryanodine receptor and other stretch activated channels that may be associated with HF-associated arrhythmias. Furthermore, we will discuss how alterations in local Ca2+ microdomains during the remodeling process associated the HF may contribute to the increased disposition for β-adrenergic or stretch induced arrhythmogenic triggers. Finally, the potential mechanisms linking β-adrenergic stimulation and mechanical stretch will be clarified, with the aim of finding common modalities of arrhythmogenesis that could be targeted by novel therapeutic agents in the setting of HF.
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