Principles of Clinical Cardiac Electrophysiology¶

Chapter 250 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 250

Key Clinical Points¶

Cardiac action potential (AP) is characterized by five distinct phases (0–4) corresponding to specific ECG segments.
Arrhythmia mechanisms are classified into three categories: automaticity, triggered activity, and reentry.
Reentry requires a combination of anatomic/functional circuit, unidirectional block, and slow conduction.
Antiarrhythmic drugs (AADs) are categorized by the Vaughan-Williams system (Classes I–IV) based on ion channel targets.
Catheter ablation targets anatomic substrates (scar, accessory pathways) or focal sources of automaticity.
Invasive electrophysiologic (EP) testing is the gold standard for defining arrhythmia mechanism and guiding ablation.
QT prolongation predisposes to early afterdepolarizations (EADs) and torsades de pointes (TdP).
Delayed afterdepolarizations (DADs) are associated with digitalis toxicity and catecholamine excess.
Functional reentry underlies atrial fibrillation and ventricular fibrillation via multiple wavefronts.
Tilt table testing (TTT) is used to diagnose neurally mediated syncope or carotid hypersensitivity.
Class IC antiarrhythmics (flecainide, propafenone) have slow binding kinetics, high potency, but can promote reentry.
Class IA agents (quinidine, procainamide) have intermediate kinetics; Class IB (lidocaine) have rapid kinetics.
The intrinsic heart rate (IHR) is the native automaticity rate of the SA node absent autonomic input.
Gap junctions formed by connexins facilitate impulse propagation between adjacent myocytes.

DEFINITION & OVERVIEW¶

• Clinical Cardiac Electrophysiology: Subspecialty focusing on the study and management of heart rhythm disorders. • Historical Perspective: ◦ 1960s: First recordings of human intracardiac electrograms (diagnostic era). ◦ 1980s: Development of radiofrequency catheter ablation (interventional era). ◦ Modern Era: Expansion into conduction system pacing, leadless pacemakers, and atrial appendage closure. ◦ Note: While procedures have evolved, the principles of arrhythmia management remain consistent.

CELLULAR ELECTROPHYSIOLOGY¶

• Action Potential (AP) Dynamics: ◦ Defined by 5 phases (0–4) that drive all cardiac myocyte behavior. ◦ ECG Correlation: ◦ Phase 0 (Rapid upstroke) → QRS deflection. ◦ Phases 1–2 → ST segment (Phase 2 is the plateau). ◦ Phase 3 → T wave (repolarization). ◦ Phase 4 → Isoelectric segment (diastole). ◦ Atrial/AV Conduction: ◦ P wave → Atrial depolarization. ◦ PR interval → Conduction through the AV node (typically most of the duration). • Ion Channels & Genetics: ◦ I_{K1} is the primary current during phase 4, determining resting membrane potential. ◦ Sodium current (I_{Na}) generates the phase 0 upstroke. ◦ Calcium current (I_{Ca,L}) and potassium currents balance to form the phase 2 plateau. ◦ Gap junctions (connexins) facilitate impulse propagation between myocytes.

Ion Channel Table¶

Table 250-1: Overview of the Mechanisms of Cardiac Tachyarrhythmias • Automaticity: ◦ Enhanced (acceleration of phase 4 repolarization) → Idiopathic VT; AT. ◦ Suppressed (absent/decelerated phase 4 repolarization) → Sinus node dysfunction. • Triggered Activity: ◦ EADs (during Phase 2/3) → TdP in long QT syndrome, PVCs. ◦ DADs (during Phase 4) → Reperfusion PVCs/VT, AT. • Reentry: ◦ Requires: (1) Anatomic or functional circuit; (2) Unidirectional block after a premature impulse; (3) Slow conduction. ◦ Examples: AVNRT, AVRT, atrial flutter, scar-related VT.

CLINICAL FEATURES¶

• Symptom Spectrum: ◦ Vague: Fatigue, chest pain, dyspnea, or lightheadedness. ◦ Specific: Rapid/slow/irregular heart rate; sensation of 'extra' or 'missed' beats (premature contractions). • Hemodynamic Impact: ◦ Impaired cardiac output → Presyncope, frank syncope, generalized weakness. ◦ Structural Heart Disease: Arrhythmias may trigger or exacerbate underlying conditions like angina, heart failure, or hypoxia-associated symptoms.

DIFFERENTIAL DIAGNOSIS¶

• Risk Stratification: Essential to determine prognosis and inform treatment aggressiveness. ◦ High hemodynamic compromise → More malignant disease → Aggressive evaluation. • Syncope Evaluation: ◦ Challenge: Distinguishing cardiac arrhythmia from benign causes. ◦ Structural abnormality of ventricular myocardium → Favors more malignant arrhythmias and lower tolerance for any arrhythmia. • Diagnostic Clues: ◦ Activity-related: Arrhythmias during exercise/stress suggest automaticity-triggered events. ◦ Medication-related: ◦ Ca channel blockers/Beta-blockers → Bradycardia. ◦ QT-prolonging drugs → TdP. ◦ Demographics: ◦ Brugada Syndrome: Strong male predominance, common in Southeast Asian populations. ◦ Inappropriate Sinus Tachycardia: Nearly exclusively young women. ◦ Degenerative Conduction Disease: Typically older patients. ◦ Atrial Fibrillation (AF): Rarely occurs in children/young adults unless associated with structural heart disease.

INVESTIGATIONS & DIAGNOSIS¶

Initial Evaluation: Directed history, physical exam, and 12-lead ECG.
Risk Stratification: Determine prognosis to dictate treatment intensity.
Structural Assessment: If structural heart disease is suspected → Echocardiography (evaluates LV function, atrial dimensions, mitral valve function).
Ischemia Evaluation: If coronary artery disease is suspected → Evaluate for ischemia.
Advanced Imaging: ◦ Cardiac CT: Evaluates ischemia, ventricular scar, anatomy, and congenital anomalies. ◦ Cardiac MRI: High resolution for soft-tissue (ischemia, infarct, cardiomyopathy, infiltrative disease). ◦ Cardiac PET: Identifies metabolic/inflammatory/infiltrative conditions.

MANAGEMENT & TREATMENT¶

Pharmacologic Strategy: ◦ Automaticity-based: Target phase 4 → Ca channel blockers, beta-adrenergic blockers. ◦ Triggered activity-based: Remove precipitating factors (e.g., remove digitalis). ◦ Reentry-based: Increase refractory period via K+ channel blocking agents OR increase heart rate to shorten QT interval.
Antiarrhythmic Drugs (Table 250-2): ◦ Class I (Na+ Blockers): ◦ IA: Quinidine, Procainamide (Intermediate kinetics). ◦ IB: Lidocaine (Rapid kinetics; used for reperfusion arrhythmias). ◦ IC: Flecainide, Propafenone (Slow kinetics; high potency; may promote reentry). ◦ Class II: Beta-adrenergic blockers. ◦ Class III: Potassium channel blockers (Amiodarone, Sotalol, Dofetilide, Dronedarone, Ibutilide). ◦ Class IV: Calcium channel blockers. ◦ Special Agents: Ranolazine (Late sodium channel blockade).
Catheter Ablation: ◦ Target Selection: Identify and ablate anatomic substrates (scar, accessory pathways) or focal sources of automaticity. ◦ Technology: ◦ Electroanatomical mapping: 3D reconstruction for real-time localization. ◦ Intracardiac Echocardiography (ICE): Real-time visualization to ensure safety during ablation.

PROGNOSIS & COMPLICATIONS¶

• Prognostic Indicators: ◦ Hemodynamic stability and presence of structural heart disease are primary indicators. ◦ Structural abnormalities → Higher risk of lethal arrhythmias and lower tolerance for treatment. • Imaging Utility: ◦ CT, MRI, and PET provide critical data on ischemia, scar tissue, and infiltrative conditions to guide long-term management.

KEY PEARLS & CLINICAL TRAPS¶

• Mechanism Link: EADs → Long QT; DADs → Digoxin/Catecholamines. ◦ Ablation Goal: Identify and isolate the anatomic substrate or focal source of automaticity. ◦ Drug Selection: Use of AADs is often an 'ancillary option' due to narrow therapeutic index and risk of proarrhythmia. ◦ FFR Threshold: ≤ 0.80 is the critical value for revascularization decision.

Reference Tables¶

TABLE 250-1 Overview of the Mechanisms of Cardiac Tachyarrhythmias¶

Harrison's 22e, p.1913

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
	DADs
Reentry	(1) Anatomic or functional confinement of a circuit (i.e., scar, accessory pathway); (2) unidirectional block after a premature impulse; (3) wave of excitation that travels in a single direction returning to its point of origin	AVNRT, AVRT, atrial flutter, scar- related VT

TABLE 250-2 Antiarrhythmic Drug Actions DRUG Quinidine Flecainide Propafenone Amiodarone Sotalol Dofetilide Dronedarone…¶

Harrison's 22e, p.1916

DRUG	CLASS ACTIONS				OTHER ACTIONS/COMMON SIDE EFFECTS
	I	II	III	IV
Quinidine	++		++		Anticholinergic
	+++		+
Propafenone	++	+			Mild beta-blocker effect
	++	++	+++	+
Sotalol		++	+++		Prominent beta-blocker effect
			+++
Dronedarone	+	+	+	+	Mild effect
			+++
Ranolazine	++		++		Late sodium channel blockade
	++