Healthy hearts at hectic pace: From daily life stress to abnormal cardiomyocyte function and arrhythmias

The hectic pace of contemporary life is a major source of acute and chronic stress, which may have a deleterious impact on body health. In the field of cardiovascular disease, acute emotional stress has been associated with coronary spasm and Takotsubo cardiomyopathy, whereas the manifestations of chronic stress have been overlooked, and most underlying pathophysiology remains to be elucidated. Chronic stress affects the neuronal circuitry composed of cortico-limbic structures and the nuclei regulating autonomic function, eliciting a sympatho-vagal imbalance, characterised by adrenergic activation and vagal withdrawal. Sympathetic terminals are connected to cardiomyocytes in a quasi-synaptic way, producing the so called ‘neuro-cardiac junction'. During chronic stress, norepinephrine release is increased, leading to overstimulation of cardiomyocytes via β₁-adrenergic receptors, influencing mainly calcium dynamics, and β₂-adrenergic receptors, which control housekeeping functions. The circadian rhythm of cardiomyocytes is then impaired, with elongation of the catabolic (‘light’ phase) over the anabolic (‘nocturnal’) phase. This leads to a depletion of cell energy storage, and a decreased turnover of cell constituents. Even cell interactions are affected, as coupling between cardiomyocytes decreases while coupling between cardiomyocytes and fibroblasts increases. The ultimate results are changes in the shape and velocity of action potential, fibroblast activation and deposition of extracellular matrix. These alterations may predispose to arrhythmias and may favour the development of a stress-related cardiomyopathy. A better comprehension of this cascade of events may allow us to identify screening protocols and treatment strategies (meditation, yoga, physical activity, psychological assistance, β-blockers) to prevent or relieve ongoing cardiac damage.