What are the causes of bradycardia (abnormally slow heart rate)?

From the Guidelines

Bradycardia is most commonly caused by reversible factors such as medications, including beta blockers, calcium channel blockers, and digoxin, as well as hypothyroidism and metabolic abnormalities like severe systemic acidosis or hypokalemia. According to the 2019 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay 1, these factors can decrease the sinus rate and exacerbate bradycardia in patients with preexisting sinoatrial node dysfunction (SND).

Common Causes of Bradycardia

• Medications: beta blockers, calcium channel blockers, digoxin, sodium-channel and potassium-channel blocking antiarrhythmic drugs
• Hypothyroidism: can cause clinically significant bradycardia, which responds well to replacement therapy with thyroxine (T4) 1
• Metabolic abnormalities: severe systemic acidosis or hypokalemia can uncommonly cause sinus bradycardia in acute settings
• Other factors: athletic training, heart disorders like sick sinus syndrome, heart block, and heart attacks that damage the heart's electrical system, sleep apnea, and inflammatory conditions like myocarditis

Importance of Identifying Reversible Causes

Identifying and treating reversible causes of bradycardia is crucial, as it can improve symptoms and quality of life for patients. The 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy 1 emphasize the importance of early identification of potentially reversible causes of bradycardia. By addressing these underlying factors, healthcare providers can determine the best course of treatment, which may include medication adjustments, treating underlying conditions, or in severe cases, pacemaker implantation.

From the FDA Drug Label

Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of metoprolol. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders may be at increased risk. Catecholamine-depleting drugs (e. g., reserpine) may have an additive effect when given with beta-blocking agents, or monoamine oxidase (MAO) inhibitors. Observe patients treated with metoprolol plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension Digitalis Glycosides and Beta-Blockers Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia Calcium channel blockers may also have an additive effect when given with atenolol. Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects. Disopyramide has been associated with severe bradycardia, asystole and heart failure when administered with beta-blockers. The causes of bradycardia include:

• Beta-blocker therapy such as metoprolol or atenolol
• Concomitant use of digitalis glycosides and beta-blockers
• Catecholamine-depleting drugs such as reserpine
• Calcium channel blockers
• Disopyramide, a Type I antiarrhythmic drug
• First-degree atrioventricular block, sinus node dysfunction, or conduction disorders 2
• Monoamine oxidase (MAO) inhibitors 2
• Concomitant administration of hydralazine may inhibit presystemic metabolism of metoprolol leading to increased concentrations of metoprolol 2
• Alpha-adrenergic Agents such as guanethidine, betanidine, reserpine, alpha-methyldopa or clonidine may be potentiated by beta-blockers including metoprolol 2
• Ergot Alkaloid concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids 2
• Dipyridamole administration of a beta-blocker should be withheld before dipyridamole testing, with careful monitoring of heart rate following the dipyridamole injection 2
• CYP2D6 Inhibitors potent inhibitors of the CYP2D6 enzyme may increase the plasma concentration of metoprolol 2

From the Research

Causes of Bradycardia

• Bradycardia can be caused by physiologic and pathologic conditions, including sinus node dysfunction and atrioventricular (AV) conduction disturbances 3
• It can also be due to sinus, atrial, or junctional bradycardia or to a problem with the conduction system (eg, an atrioventricular block) 4
• Pathology that produces bradycardia may occur within the sinus node, atrioventricular (AV) nodal tissue, and the specialized His-Purkinje conduction system 5
• Electrolyte disorders, such as hypokalemia and hyperkalemia, can alter cardiac ionic currents kinetics and promote proarrhythmic or antiarrhythmic effects, leading to bradycardia 6
• Certain medical conditions, such as hypothyroidism, can also cause bradycardia, with symptoms including fatigue, lethargy, and cold intolerance 7

Underlying Causes

• Sinoatrial node dysfunction
• Atrioventricular (AV) conduction disturbances
• Electrolyte disorders (e.g. hypokalemia, hyperkalemia)
• Hypothyroidism
• Other medical conditions that affect the heart rate

Risk Factors

• Age
• Sex
• Presence of underlying medical conditions (e.g. heart disease, thyroid disorders)
• Certain medications that can affect heart rate
• Electrolyte imbalances 6