What are the possible causes of an unexplained elevated heart rate (tachycardia)?

Unexplained Elevated Heart Rate: Causes and Diagnostic Approach

Unexplained elevated heart rate (tachycardia) is most commonly caused by reversible physiological or pathological triggers including infection with fever, dehydration, anemia, hyperthyroidism, heart failure, exogenous substances (caffeine, beta-agonists, illicit stimulants), pain, anxiety, and medications—all of which must be systematically excluded before considering primary cardiac arrhythmias or inappropriate sinus tachycardia. 1

Primary Systematic Evaluation

Reversible Physiological and Pathological Causes

The cornerstone of evaluation is identifying and treating secondary causes, as these account for the vast majority of unexplained tachycardia cases. 1, 2

• Infection and fever: Fever increases metabolic demands and triggers compensatory tachycardia through normal autonomic responses 1
• Dehydration and hypovolemia: Volume depletion causes reflex tachycardia to maintain cardiac output 1, 2
• Anemia: Reduced oxygen-carrying capacity necessitates increased heart rate to maintain tissue perfusion 1, 2
• Hyperthyroidism: Excess thyroid hormone directly increases sinus node automaticity and sympathetic tone 1, 2
• Heart failure: Compensatory tachycardia develops to maintain cardiac output in the setting of reduced ventricular function 1
• Pain: Inadequate analgesia triggers catecholamine release and sympathetic activation 2
• Pulmonary embolism: A life-threatening cause that must be considered, particularly with acute onset 2

Exogenous Substances and Medications

A comprehensive medication and substance use history is mandatory, as these are frequently overlooked reversible triggers. 1, 2

• Stimulants: Caffeine, nicotine, illicit drugs (cocaine, amphetamines, methamphetamine), and cannabis 1, 2
• Medications: Beta-agonist bronchodilators (albuterol), aminophylline, atropine, catecholamines, anticancer agents (particularly anthracyclines) 1, 2
• Alcohol: Can trigger tachycardia both acutely and during withdrawal 1

Psychological and Autonomic Causes

Emotional stress and anxiety disorders are extremely common but frequently misdiagnosed causes of tachycardia, leading to extensive unnecessary cardiac testing. 1

• Anxiety and panic disorders: Trigger physiological sinus tachycardia through normal catecholamine-driven mechanisms 1, 2
• Autonomic dysfunction: Including postural orthostatic tachycardia syndrome (POTS), characterized by heart rate increase ≥30 bpm within 10 minutes of standing without orthostatic hypotension 3
• Somatic hypervigilance: Cognitive and behavioral factors contribute to symptom chronicity in many patients 3

Primary Cardiac Arrhythmias

After excluding secondary causes, consider primary supraventricular and ventricular arrhythmias as potential etiologies. 4, 1

Supraventricular Tachycardias

• Atrioventricular nodal reentrant tachycardia (AVNRT): The most common reentry mechanism producing accelerated heart rates with abrupt onset and termination 1, 5
• Atrioventricular reentrant tachycardia (AVRT): Involves accessory pathways, including Wolff-Parkinson-White syndrome 1
• Atrial tachycardia: Arises from localized atrial sites, can be focal or multifocal 1
• Atrial flutter: Represents macroreentrant atrial tachycardia 1
• Sinus node reentry tachycardia: Causes abrupt onset and termination, distinguishing it from physiological sinus tachycardia 1

Ventricular Arrhythmias

Ventricular couplets, triplets, and non-sustained ventricular tachycardia always require investigation as markers for underlying cardiac pathology. 1

• Premature ventricular contractions (PVCs): Present in <1% of athletes but may indicate underlying heart disease, particularly when ≥2 PVCs appear on ECG 1
• Among patients with ≥2,000 PVCs per 24 hours, up to 30% have underlying structural heart disease 1

Inappropriate Sinus Tachycardia (IST)

IST is a diagnosis of exclusion, defined as sinus tachycardia unexplained by physiological demands with resting heart rate >100 bpm and average 24-hour rate >90 bpm, accompanied by debilitating symptoms. 1, 2, 6

Diagnostic Criteria

• Resting heart rate >100 bpm or average 24-hour rate >90 bpm 1, 2
• Associated symptoms: Weakness, fatigue, lightheadedness, palpitations, sensation of heart racing 1, 2
• Exclusion of all secondary causes is mandatory before diagnosis 1, 2, 6

Proposed Mechanisms

• Dysautonomia and neurohormonal dysregulation 1
• Intrinsic sinus node hyperactivity 1
• Enhanced sinus node automaticity with increased sympathetic or reduced parasympathetic activity 7
• Autoantibodies to beta-adrenergic receptors have been observed in some patients 7

Structured Diagnostic Algorithm

Step 1: Confirm True Tachycardia

• Obtain 12-lead ECG during tachycardia to distinguish supraventricular from ventricular origins and assess QRS width 1, 2
• Verify sinus rhythm: P waves positive in leads I, II, aVF; negative in aVR; normal P-wave morphology preceding each QRS 2
• If resting sinus tachycardia >120 bpm, repeat ECG after rest to exclude recent exercise or anxiety 1

Step 2: Assess for Hemodynamic Instability

• Evaluate for rate-related cardiovascular compromise: Acute altered mental status, ischemic chest discomfort, acute heart failure, hypotension, or shock 2
• If unstable, proceed to immediate synchronized cardioversion 2

Step 3: Systematic Exclusion of Secondary Causes

• Check oxygen saturation and provide supplemental oxygen if inadequate 2
• Assess for infection: Fever, inflammatory markers 2
• Review hemoglobin levels for anemia 2
• Check thyroid function tests for thyrotoxicosis 2
• Evaluate for dehydration/hypovolemia: Clinical signs, orthostatic vital signs 2
• Consider pulmonary embolism in appropriate clinical context 2
• Assess pain control and acute stressors 2
• Review all medications and substances: Stimulants, beta-agonists, aminophylline, catecholamines, illicit drugs 2

Step 4: Evaluate for Structural Heart Disease

• Obtain echocardiogram to assess for cardiomyopathies, valvular disease, and ventricular function 4
• Consider coronary artery disease, particularly in patients ≥30 years of age 1

Step 5: Extended Monitoring if Diagnosis Unclear

• Holter monitor or event recorder to capture arrhythmia and confirm diagnosis 5
• Electrophysiology study (EPS) may be considered in selected patients with unexplained syncope or presyncope when noninvasive evaluation is nondiagnostic 4

Critical Pitfalls to Avoid

• Do not assume IST without excluding all physiologic causes, as true IST is rare and a diagnosis of exclusion 2
• Do not misdiagnose anxiety or panic disorder without proper cardiac evaluation, as this leads to delayed diagnosis of true arrhythmias 5
• Do not use rate-controlling medications in patients with accessory pathways (WPW syndrome), as this can accelerate conduction through the accessory pathway 2
• Do not repeatedly order cardiac testing in patients with multiple negative evaluations; instead, refer for cognitive-behavioral therapy 1
• Avoid initiating class I or III antiarrhythmic drugs without documented arrhythmia due to proarrhythmic risk 1

Management Principles

The mainstay of management involves identifying and eliminating or treating the underlying cause rather than simply normalizing the heart rate. 1, 2

For Secondary Causes

• Treat the underlying condition: Antibiotics for infection, fluid resuscitation for dehydration, iron supplementation or transfusion for anemia, antithyroid medications for hyperthyroidism 2
• Discontinue offending agents: Stimulants, beta-agonists, and other triggering medications 2

For Anxiety-Related Tachycardia

• Beta-blockers are first-line for anxiety-related tachycardia and provide effective symptom control 1, 2
• Cognitive-behavioral therapy demonstrates clear benefit, reducing symptom frequency by 32% over 3 months in patients with recurrent symptoms despite negative cardiac workup 1

For Inappropriate Sinus Tachycardia

• Ivabradine is reasonable for ongoing management in symptomatic IST (Class IIa recommendation), as it selectively reduces sinus node activity 2, 6
• Beta-blockers may be considered (Class IIb recommendation), though often ineffective or poorly tolerated due to hypotension 2
• Combination of beta-blockers and ivabradine may be considered for refractory cases (Class IIb recommendation) 2
• Exercise training may be beneficial but efficacy remains unproven 2