What is the pathophysiologic mechanism by which stress induces cardiac palpitations?

Mechanism of Stress-Induced Heart Palpitations

Stress causes heart palpitations primarily through a catecholamine surge—specifically elevated norepinephrine and epinephrine—that activates cardiac β-adrenergic receptors, increasing heart rate and contractility while simultaneously altering cardiac autonomic tone and triggering ectopic electrical activity. 1

Primary Pathophysiologic Pathway

Sympathetic Nervous System Activation

• Acute psychological or physical stress activates the sympathetic-adrenal-medullary (SAM) axis, releasing catecholamines (norepinephrine from sympathetic nerve terminals and epinephrine from the adrenal medulla) into circulation 2, 3
• Mean norepinephrine levels increase significantly during stress, with studies demonstrating that >50% rises in plasma norepinephrine correlate with more severe cardiac electrical disturbances 1
• This catecholamine release occurs within minutes of stress exposure, with measurable elevations in salivary amylase (a surrogate marker for norepinephrine) and direct plasma measurements during stressful activities 1

Direct Cardiac Effects

• Catecholamines bind to β1-adrenergic receptors on cardiomyocytes, increasing heart rate, contractility, and automaticity through enhanced calcium handling 2
• Enhanced sympathetic activity increases cardiac automaticity and triggers ectopic beats by promoting abnormal calcium movements in cardiomyocytes 1, 2
• At supraphysiologic concentrations, catecholamines can induce intracellular calcium overload, leading to afterdepolarizations and triggered arrhythmias that patients perceive as palpitations 2

Secondary Mechanisms Contributing to Palpitations

Autonomic Imbalance

• Stress simultaneously activates sympathetic outflow while inhibiting vagal (parasympathetic) tone, removing the protective dampening effect on heart rate and creating conditions favorable for arrhythmias 4
• This autonomic imbalance alters cardiac ion channel function, particularly affecting connexin 40 and connexin 43 expression, which enhances myocardial vulnerability to ectopic activity and re-entry circuits 1

Electrical Remodeling

• Sympathetic activation causes prolongation and dispersion of ventricular repolarization, creating electrical heterogeneity that predisposes to premature beats and arrhythmias 1
• Anger and emotional stress specifically increase the frequency of ventricular arrhythmias, with one study showing anger in the 15 minutes prior to arrhythmia events had an odds ratio of 1.83 compared to control periods 1

Oxidative Stress Pathway

• High concentrations of catecholamines undergo oxidation to form aminolutins and generate oxygen radicals, which directly damage myocardial cells and induce calcium-handling abnormalities 2
• These oxidation products can produce coronary spasm and arrhythmias by affecting both sarcolemmal and sarcoplasmic reticulum function 2

Regional Cardiac Vulnerability

Differential Receptor Distribution

• The ventricular apex has increased β2-adrenergic receptor density despite relatively sparse sympathetic innervation, explaining why stress-related electrical disturbances can manifest with regional variation 5, 6
• β2-adrenergic receptors undergo signaling switch from Gs to Gi protein signaling at high epinephrine levels, causing negative inotropy but paradoxically protecting against apoptosis while still generating arrhythmogenic substrate 5, 6

Stress-Specific Considerations

Emotional vs. Physical Triggers

• Both emotional stressors (grief, fear, anger) and physical stressors (acute illness, surgery) activate the same catecholamine-mediated pathway, though emotional triggers may produce more regionalized cardiac sympathetic responses 5, 6, 4
• Laboratory mental stress produces regionalized sympathetic nervous responses directed specifically to the heart while sparing sympathetic outflow to skeletal muscle vasculature 4

Glucocorticoid Amplification

• Stress-induced glucocorticoid release amplifies catecholamine effects by inhibiting extraneuronal catecholamine uptake and upregulating β-adrenoceptor signal transduction components 2
• This glucocorticoid-catecholamine interaction creates supersensitivity to catecholamines in cardiac tissue, magnifying the arrhythmogenic potential of even modest stress responses 2

Clinical Implications

Vulnerable Populations

• Patients with pre-existing psychiatric disorders (anxiety, depression) show amplified stress responses and increased susceptibility to stress-induced cardiac electrical disturbances 5, 6
• Postmenopausal women are particularly vulnerable, with estrogen deficiency potentially increasing sensitivity to catecholamine-mediated cardiac effects 5

Extreme Manifestations

• In severe cases, supraphysiological catecholamine surges can produce stress-induced (Takotsubo) cardiomyopathy, representing the extreme end of the stress-palpitation spectrum with documented astronomically high plasma adrenaline concentrations 7, 5, 4
• The mechanism involves the same catecholamine pathway but at concentrations that produce myocardial stunning rather than just palpitations 7, 5

Negative Feedback Mechanisms

• Vagal sensory fibers are directly activated by epinephrine and norepinephrine, representing an afferent limb of a negative feedback loop that attempts to adjust sympathoadrenal system activity according to plasma catecholamine levels 8
• This feedback mechanism explains why palpitations are typically self-limited once the acute stressor resolves, though chronic stress can dysregulate this homeostatic system 8, 9