Atrial Fibrillation¶
Chapter 258 | Harrison's 22e · Part 6 – Cardiovascular Disorders · Chapter 258
Key Clinical Points¶
- Atrial fibrillation (AF) is the most common sustained arrhythmia, characterized by disorganized, rapid, and irregular atrial electrical activation resulting in a loss of organized atrial mechanical contraction.
- Clinical classification (Paroxysmal, Persistent, Long-standing Persistent) correlates with underlying pathophysiology, such as left atrial (LA) size and scar burden, and determines the expected efficacy of pharmacological or ablation therapies.
- Risk factors include age, alcohol use, obesity, hypertension, diabetes mellitus, and sleep-disordered breathing.
- AF is a significant public health issue: it increases mortality by 1.5- to 1.9-fold (adjusted for underlying disease) and accounts for approximately 25% of all strokes.
- Pathophysiology involves a 'final common pathway' where risk factors lead to electrophysiologic changes, notably enhanced automaticity in the pulmonary vein musculature.
- Diagnosis is primarily confirmed via ECG (absence of P waves, irregularly irregular R-R intervals), with advanced monitoring and wearable devices increasingly used for screening.
- Management involves balancing stroke risk (CHA₂DS₂-VASc) against bleeding risk (HAS-BLED) to guide anticoagulation, with specific dosing adjustments for NOACs based on age, weight, and renal function.
- Pulsed-field ablation (PFA) is an emerging technique that utilizes high-voltage, short-duration pulses to selectively ablate myocardium while sparing adjacent tissues like nerves and the esophagus due to differing tissue breakdown thresholds.
DEFINITION & CLASSIFICATION¶
• Atrial Fibrillation (AF): A cardiac arrhythmia characterized by disorganized, rapid, and irregular atrial electrical activation, resulting in a loss of organized atrial mechanical contraction. • Clinical Classification (Table 258-1): • Paroxysmal AF: → Definition: Episodes self-terminate or are terminated via pharmacologic, medical, or electrical cardioversion in <7 days. → LA size: Normal to mildly enlarged. → LA scar burden: Low. → Efficacy of AAD: Often effective. → Ablation Strategy: Pulmonary vein (PV) isolation alone is usually effective; first-line therapy is reasonable. • Persistent AF: → Definition: Episodes lasting >7 days but <1 year. → LA size: Mild to severely enlarged. → LA scar burden: Moderate. → Efficacy of AAD: Not as effective. → Ablation Strategy: First-line not appropriate but usually offered after AAD failure; includes PV isolation and any identified non-PV AF source. • Long-standing Persistent AF: → Definition: Persistent AF >1 year. → LA size: Typically, severely enlarged. → LA scar burden: High. → Efficacy of AAD: Usually refractory. → Ablation Strategy: After AAD failure, not always a good option; includes PV isolation and additional ablation for substrate modification.
EPIDEMIOLOGY¶
• Prevalence: → Increases with age; >95% of patients are >60 years old; ~20% in humans over 80. → Lifetime risk for men aged 40 is approximately 25%. → Slightly more common in men than women; more common in whites than blacks. • Risk Factors: → Age, alcohol use, obesity, hypertension, diabetes mellitus, cardiac disease, family history of AF, and sleep-disordered breathing.
ETIOLOGY & PATHOPHYSIOLOGY¶
• Pathophysiology Concept: A "final common pathway" where various risk factors lead to electrophysiologic changes in atrial tissues. • Electrophysiological Changes: → Alterations in regulation of membrane channels and other proteins → abnormal electrical excitability. → Pulmonary vein musculature: Exhibit enhanced automaticity, resulting in ectopic beats (premature atrial contractions). → Bouts of rapid atrial ectopy may initiate either atrial tachycardia or frank AF. → Tissue remodeling: Results in abnormal conduction properties, including shortening of atrial tissue refractory periods. • Structural Remodeling: → Leads to development of fibrosis and left atrial enlargement (Table 258-1). • Clinical Progression: → Patients often experience sporadic ectopic beats and short runs of atrial tachycardia (likely from pulmonary veins) preceding the onset of frank AF. → As remodeling progresses, the efficacy of therapeutic interventions to restore sinus rhythm diminishes.
CLINICAL FEATURES¶
• Clinical Manifestations: 1. Symptoms related to irregular, often rapid but sometimes slow ventricular rates. 2. Hemodynamic consequences of altered cardiac function. 3. Consequences of cardioembolic phenomena. 4. Impact of AF on cardiovascular function over time. • Symptoms: Palpitations (awareness of the heartbeat in a normal rhythm). • Risks & Complications: → Mortality: 1.5- to 1.9-fold increased risk after controlling for underlying cardiac disease. → Stroke: Significantly increased risk; approximately 25% of all strokes are caused by AF. → Dementia: Increased risk in patients with AF. → Embolic Events: Increased risk of MRI-detected asymptomatic embolic infarct. → Heart Failure: Risk increases with prolonged, uncontrolled ventricular rates (leading to heart failure and cardiomyopathy). → Detection: Up to 8.9% of patients identified within 6 months following cryptogenic stroke using insertable cardiac monitors.
DIAGNOSTIC APPROACH¶
- Electrocardiogram (ECG): → Standard 12-lead ECG: Identify lack of organized atrial activity (no P wave) and irregularly irregular ventricular response. → Lead V1: Best shows disorganized atrial activation.
- Monitoring Devices: → Limited lead ambulatory monitor ECG. → Implantable loop recorders. → Wearable monitors and home ECG capabilities (increasing role in screening populations).
MANAGEMENT & TREATMENT¶
- Anticoagulation Risk Assessment: → Use CHA₂DS₂-VASc to assess stroke risk. → Use HAS-BLED to assess bleeding risk.
- Novel Oral Anticoagulant (NOAC) Dosing (Table 258-2): • Dabigatran: → Standard: 150 mg bid. → Reduced (110 mg bid): If age ≥ 80 years, concurrent use of verapamil, or increased bleeding risk. • Rivaroxaban: → Standard: 20 mg qd. → Reduced (15 mg qd): If Creatine clearance 15–49 mL/min. • Apixaban: → Standard: 5 mg bid. → Reduced (2.5 mg bid): If at least 2 of 3 criteria met: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL (133 mol/L). • Edoxaban: → Standard: 60 mg qd. → Reduced: If any of the following: creatinine clearance 30–50 mL/min, body weight ≤ 60 kg, or concomitant use of dronedarone, cyclosporine, erythromycin, or ketoconazole.
- Ablation Strategy (Table 258-1): • Paroxysmal AF: → PV isolation alone usually effective; first-line therapy reasonable. • Persistent AF: → First-line not appropriate but usually offered after AAD failure; strategy includes PV isolation and any identified non-PV AF source. • Long-standing Persistent AF: → After AAD failure, not always a good option; requires PV isolation and additional ablation for substrate modification.
- Pulsed-Field Ablation (PFA) (Figure 258-5): → Mechanism: Uses high-voltage, short-duration electrical pulses to create pores in cell membranes (electroporation). → Advantage: Selectively targets myocardial tissue (threshold 375 V/cm) while sparing adjacent structures due to higher breakdown thresholds: red blood cells (1600 V/cm), endothelium (1750 V/cm), and nerves (3800 V/cm).
KEY PEARLS & HIGH-YIELD POINTS¶
• Risk Scoring: → CHA₂DS₂-VASc: Includes Heart Failure, Hypertension, Age ≥ 75, Diabetes, Prior Stroke/TIA, Vascular Disease, Age ≥ 65, and Female sex. → HAS-BLED: Includes Hypertension, Abnormal renal/liver function, Stroke history, Bleeding diathesis, Labile INR, Elderly (Age >65), and Drugs/Alcohol. • Clinical Significance: → AF is not a benign condition; it is a major public health issue due to stroke risk. → Pulmonary vein musculature is the primary site of increased automaticity leading to ectopic beats.
Reference Tables¶
TABLE 258-2 Novel Oral Anticoagulant Dosing Standard dose Reduced dose Dose reduction criteria¶
Harrison's 22e, p.1951
| DABIGATRAN | RIVAROXABAN | APIXABAN | EDOXABAN | |
|---|---|---|---|---|
| Standard dose | 150 mg bid | 20 mg qd | 5 mg bid | 60 mg qd |
| 110 mg bid | 15 mg qd | 2.5 mg bid | ||
| Dose reduction criteria | Dabigatran 110 mg bid in patients with: age ≥80 years, concomitant use of verapamil, or increased bleeding risk |
Creatine clearance 15–49 mL/min |
At least 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 mol/L) |
If any of the following: creatinine clearance 30–50 mL/min, body weight ≤60 kg, or concomitant use of dronedarone, cyclosporine, erythromycin, or ketoconazole |