Principles of Clinical Cardiac Electrophysiology¶
Chapter 250 | Part 6: Disorders of the Cardiovascular System
KEY CLINICAL POINTS¶
- Cardiac action potentials (APs) drive electrophysiologic behavior, with distinct phases (0–4) corresponding to depolarization, repolarization, and diastole.
- Ion channels (Na, Ca, K) and their genetic subunits (e.g., SCN5A, KCNQ1) underpin AP morphology and arrhythmia mechanisms.
- Reentry, triggered activity (EADs/DADs), and enhanced automaticity are primary mechanisms of cardiac arrhythmias.
- Antiarrhythmic drugs (Vaughan-Williams classification) and catheter ablation are cornerstone treatments for arrhythmias.
- Electrophysiology studies and imaging (e.g., intracardiac echocardiography) guide diagnosis and ablation of arrhythmias.
1. DEFINITION & OVERVIEW¶
Clinical cardiac electrophysiology is a subspecialty focusing on heart rhythm disorders. It integrates cellular electrophysiology, ion channel function, and arrhythmia mechanisms. The field evolved from early ECG recordings to modern catheter ablation and device therapy.
Table 250-1: Mechanisms of Cardiac Tachyarrhythmias¶
| TACHYARRHYTHMIA CATEGORY | MECHANISM | PROTOTYPICAL ARRHYTHMIAS |
|---|---|---|
| Abnormal Automaticity | Enhanced (acceleration of phase 4 repolarization) | Idiopathic VT; AT |
| Suppressed (absent or decelerated phase 4 repolarization) | Sinus node dysfunction | |
| EADs | TdP in long QT, PVCs | |
| DADs | Reperfusion PVCs/VT, digitalis toxicity | |
| Reentry | (1) Anatomic or functional confinement of a circuit | AVNRT, AVRT, atrial flutter, scar-related VT |
| (2) Unidirectional block after a premature impulse | ||
| (3) Wave of excitation returning to its point of origin |
1.1 Cellular Electrophysiology¶
The cardiac action potential (AP) drives electrical activity. Atrial and ventricular APs have distinct ionic currents (Na, Ca, K) and phases (0–4). The ECG reflects these phases: QRS (phase 0), ST (phase 2), T wave (phase 3), and isoelectric segment (phase 4).
1.2 Historical Perspective¶
Modern cardiac electrophysiology began with ECG development by Einthoven. Key milestones include intracardiac electrogram recordings, antiarrhythmic drug development, and catheter ablation in the 1980s. Implantable devices (pacemakers, defibrillators) established it as a distinct subspecialty.
2. EPIDEMIOLOGY¶
Arrhythmias are common, with prevalence increasing with age. Atrial fibrillation (AF) is most prevalent, affecting ~1 in 5 adults over 80 years. Ventricular tachycardia (VT) and sudden cardiac death (SCD) are more common in males and those with structural heart disease. QT prolongation syndromes (e.g., Brugada) have variable prevalence across ethnic groups.
2.1 Risk Factors¶
Age, hypertension, ischemic heart disease, diabetes, electrolyte imbalances (hypokalemia, hypomagnesemia), and genetic predispositions (e.g., Brugada syndrome, long QT syndrome) increase arrhythmia risk.
2.2 Demographics¶
AF is rare in children but common in older adults. Brugada syndrome is more prevalent in Southeast Asians. Inappropriate sinus tachycardia affects young women. Degenerative conduction disease is common in older patients.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Arrhythmias arise from ion channel dysfunction, structural heart disease, or autonomic imbalance. Key mechanisms include reentry, triggered activity (EADs/DADs), and enhanced automaticity. Genetic mutations (e.g., KCNQ1, SCN5A) underlie inherited channelopathies.
Table 250-2: Antiarrhythmic Drug Actions¶
| DRUG | CLASS ACTIONS | OTHER ACTIONS/COMMON SIDE EFFECTS |
|---|---|---|
| Quinidine | I (+++), III (++) | Anticholinergic |
| Propafenone | I (+++), III (+) | Mild beta-blocker effect |
| Sotalol | II (+++), III (+++) | Prominent beta-blocker effect |
| Dronedarone | I (+), III (+), IV (+) | Mild effect |
| Ranolazine | I (+++), II (++) | Late sodium channel blockade |
3.1 Ion Channel Dysfunction¶
Na, Ca, and K channels regulate AP phases. Mutations in these channels cause long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic VT. Drug interactions (e.g., antiarrhythmics, digitalis) can exacerbate these conditions.
3.2 Reentry Mechanisms¶
Reentry occurs via anatomic barriers (e.g., scar tissue) or functional block (e.g., accessory pathways). It requires unidirectional block and slow conduction to sustain arrhythmia. Functional reentry drives AF and VF.
3.3 Triggered Activity¶
Early afterdepolarizations (EADs) occur in prolonged QT intervals (e.g., long QT syndrome). Delayed afterdepolarizations (DADs) result from intracellular Ca overload, often seen in ischemia or digitalis toxicity.
4. CLINICAL FEATURES¶
Symptoms vary by arrhythmia type: palpitations, syncope, chest pain, or fatigue. Tachycardia may cause hemodynamic instability, while bradycardia may lead to syncope. ECG findings include P wave abnormalities, QRS morphology, and QT prolongation.
4.1 Tachyarrhythmias¶
Atrial fibrillation (AF) presents with irregularly irregular rhythm and possible thromboembolic risk. Ventricular tachycardia (VT) may cause hemodynamic compromise or syncope. Supraventricular tachycardia (SVT) often presents with sudden onset and palpitations.
4.2 Bradyarrhythmias¶
Sinus bradycardia or heart block may cause syncope, fatigue, or dizziness. AV block (first-degree, Mobitz I/II, complete) requires evaluation for underlying conduction system disease.
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnosis includes electrolyte disturbances, myocardial ischemia, drug toxicity (e.g., digitalis), and structural heart disease. Non-cardiac causes of syncope (e.g., neurally mediated, orthostatic hypotension) must be excluded.
5.1 Syncope¶
Cardiac vs. non-cardiac causes: syncope from arrhythmias (e.g., VT, AF) vs. vasovagal, orthostatic, or neurological etiologies. Tilt table testing (TTT) may help differentiate autonomic-mediated syncope.
5.2 ECG Findings¶
QT prolongation (long QT syndrome), preexcitation (WPW), bundle branch blocks, and ST/T wave abnormalities guide differential diagnosis.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis combines ECG, ambulatory monitoring (Holter, event recorder), and electrophysiology studies (EPS). Imaging (echo, CMR, CT) assesses structural heart disease. Fractional flow reserve (FFR) guides revascularization decisions.
6.1 Diagnostic Tests¶
12-lead ECG, Holter monitoring, event recorders, and EPS (with programmed stimulation) identify arrhythmia mechanisms. Intracardiac echocardiography (ICE) enhances ablation safety.
6.2 Imaging¶
Echocardiography evaluates structural heart disease. Cardiac MRI detects scar, infarction, or infiltrative disease. CT identifies coronary artery anomalies or congenital defects.
7. MANAGEMENT & TREATMENT¶
Treatment depends on arrhythmia type and severity. Pharmacologic agents (AADs) and catheter ablation are first-line for most arrhythmias. Pacemakers and defibrillators manage bradyarrhythmias and sudden cardiac death (SCD).
7.1 Antiarrhythmic Drugs¶
Class I (Na channel blockers): flecainide, propafenone. Class II (beta-blockers): sotalol. Class III (K channel blockers): amiodarone, dofetilide. Class IV (Ca channel blockers): verapamil, diltiazem.
7.2 Catheter Ablation¶
Radiofrequency (RF) ablation targets arrhythmogenic substrates (e.g., accessory pathways, scar tissue). Electroanatomic mapping guides ablation. Ablation is effective for SVT, AF, VT, and WPW.
7.3 Devices¶
Pacemakers for bradycardia. ICDs for high-risk VT or SCD. Leadless pacemakers and subcutaneous ICDs reduce complications.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis depends on arrhythmia type, underlying disease, and treatment. Complications include sudden cardiac death, thromboembolism, and drug toxicity. Long-term management requires monitoring and lifestyle modifications.
8.1 Mortality¶
VT and AF increase risk of SCD. Long QT syndrome and Brugada syndrome may cause sudden death. Effective treatment (ablation, ICDs) improves survival.
8.2 Drug Toxicity¶
Antiarrhythmics may cause proarrhythmia, QT prolongation, or systemic toxicity (e.g., amiodarone). Digitalis toxicity leads to DADs and arrhythmias.
9. SPECIAL CONSIDERATIONS¶
Pregnancy requires careful drug selection (e.g., beta-blockers, calcium channel blockers). Pediatric arrhythmias (e.g., WPW, congenital heart disease) require specialized management. Elderly patients face higher risks of drug toxicity and comorbidities.
9.1 Pregnancy¶
Avoid drugs with teratogenic risk (e.g., amiodarone). Monitor for fetal arrhythmias. Consider ablation for symptomatic arrhythmias.
9.2 Pediatrics¶
Congenital heart disease and channelopathies (e.g., Brugada, long QT) are common. Catheter ablation is safe in children. Avoid digitalis in neonates.
10. KEY POINTS & CLINICAL PEARLS¶
- Ion channels (Na, Ca, K) govern AP phases and arrhythmia mechanisms. 2. Reentry, triggered activity, and enhanced automaticity are primary arrhythmia mechanisms. 3. Antiarrhythmic drugs (Vaughan-Williams classification) and ablation are mainstays. 4. ECG and EPS guide diagnosis. 5. Device therapy (ICDs) reduces SCD risk in high-risk patients.