What is the physiology and management of electrical alternans?

Electrical Alternans: Physiology and Clinical Significance

Definition and Core Physiology

Electrical alternans represents beat-to-beat alternation in cardiac electrical properties at the cellular level, arising when heart rate exceeds the capacity of cardiac cells to cycle intracellular calcium, creating electrical heterogeneities between neighboring myocytes that directly promote arrhythmogenesis. 1

Cellular Mechanisms

• T-wave alternans reflects repolarization alternans at the single-cell level, occurring when cardiac cells cannot adequately manage calcium cycling at elevated heart rates 1
• The phenomenon is rate-dependent and manifests at relatively lower heart rates (105-110 bpm) in patients susceptible to life-threatening ventricular arrhythmias 1
• Alternans amplifies electrical heterogeneities between neighboring cardiac cells, creating the substrate for reentrant arrhythmias 1
• The alternation can involve action potential duration, conduction velocity, and intracellular calcium concentrations 2

Types of Alternans

Two distinct forms exist with different clinical implications:

• Microvolt T-wave alternans: Subtle repolarization changes (>1.9 μV) detectable only with specialized equipment, associated with arrhythmic risk stratification 1
• Macroscopic electrical alternans: Visible beat-to-beat variation in QRS amplitude/axis, classically associated with large pericardial effusion and cardiac tamponade 3, 4

Critical distinction: Macroscopic alternans with pericardial effusion results from mechanical heart rotation in fluid, not true electrical conduction alternation, whereas microvolt alternans represents genuine cellular electrical instability 5

Arrhythmogenic Mechanisms

Alternans plays a causative—not merely associative—role in acute arrhythmogenesis through several mechanisms:

• Creates dispersion of refractoriness between adjacent myocardial regions, enabling wave break and reentry 6
• Deficiencies in calcium transport processes at the subcellular level generate the conditions necessary for arrhythmia onset 6
• Can be concordant (uniform alternation across myocardium) or discordant (spatially out-of-phase regions), with discordant alternans being the most deadly form 2
• The voltage-calcium relationship can be positive or negative, creating complex interactions that promote instability 2

Clinical Risk Stratification

Testing Methodology

Exercise-induced T-wave alternans testing is superior to pacing-induced testing for arrhythmic risk prediction 1:

• Target heart rate: 105-110 bpm in adults 1
• Positive test: >1.9 μV alternans with K-score >3 sustained for >2 minutes 1
• Requires special high-resolution electrodes and spectral analysis using Fast Fourier Transform 1
• Maintain chronic medications (including beta-blockers) during testing per current recommendations 1

Prognostic Value

T-wave alternans predicts sudden cardiac death and major arrhythmic events as well as or better than LVEF, electrophysiological testing, and other markers 1:

• Negative test confers low risk for sudden cardiac death across multiple studies 1
• Hazard ratio for 2-year mortality: 4.8 for abnormal T-wave alternans versus 1.5 for prolonged QRS duration 1
• Meta-analysis showed relative risk of 2.42 in ischemic heart failure and 3.67 in nonischemic heart failure 1
• Predicts risk in both coronary artery disease and dilated cardiomyopathy populations 1

Test Result Classification

Three categories with distinct prognostic implications:

• Positive: Meets voltage/duration criteria; 12.3% 2-year event rate 1
• Negative: Below threshold; 2.5% 2-year event rate 1
• Indeterminate (20-40% of tests): Due to excessive ectopy (32%), inability to reach target heart rate (51%), or nonsustained alternans (10%); 17.5% 2-year event rate—similar to positive tests 1

Critical pitfall: Indeterminate results carry similar poor prognosis as positive tests and should be managed as high-risk 1

Associated Pathological Conditions

Structural Heart Disease

• Dilated cardiomyopathy: Increased sympathetic nerve activity provokes T-wave alternans 1
• Hypertrophic cardiomyopathy: Fiber disarray and fibrosis correlate with alternans occurrence and ventricular tachyarrhythmias 1
• Both ischemic and nonischemic cardiomyopathy show significant event rates with abnormal alternans 1

Acute Conditions

• Cardiac tamponade: Macroscopic alternans is the classic association, though not always present 3, 4
• Acute ischemia and Prinzmetal's angina: Can precipitate visible alternans 5
• Long QT syndrome: High incidence of alternans, especially during emotional stress, with very high sudden death risk 5

Management Implications

Risk-Based Intervention

Abnormal T-wave alternans identifies patients most likely to benefit from ICD therapy:

• Better predictor than QRS duration for ICD benefit in patients with LVEF ≤30% 1
• Negative alternans with ischemia: Patients most likely to benefit from revascularization for survival 1
• Positive or indeterminate results warrant aggressive risk factor modification and consideration for primary prevention ICD 1

Monitoring Strategy

• Reproducibility is moderate: 65-75% concordance on repeat testing overall, 80-90% when only determinate results considered 1
• Serial testing may be warranted in borderline cases or when clinical status changes 1
• Acute surges in alternans may predict impending arrhythmia onset, opening potential for upstream antiarrhythmic intervention 6

Key Clinical Caveats

• Electrical alternans is a sign, not a diagnosis—requires comprehensive evaluation for underlying etiology 4
• Atrial fibrillation and frequent ectopy prevent accurate testing 1
• Historical mortality of 62% with visible alternans underscores its serious prognostic implications 5
• The phenomenon represents a potentially reversible overture to arrhythmogenesis, suggesting therapeutic targets in calcium handling pathways 6