243: PRINCIPLES OF CLINICAL CARDIAC • Voltage-sensing segment: S4 segment (contains charged
ELECTROPHYSIOLOGY amino acids).
• Selectivity: Determined by amino acid composition in the P
HISTORICAL PERSPECTIVE OF CARDIAC ELECTROPHYSIOLOGY domain.
• Definition: Clinical cardiac electrophysiology is a cardiology Types of Channel Architecture
subspecialty focused on diagnosing and managing heart Channel Type Structure
rhythm disorders (arrhythmias). Voltage-gated K⁺ 4 separate homologous α subunits
• Key Historical Milestones:
Voltage-gated Na⁺/Ca²⁺ 1 α subunit with 4 homologous domains
o Early 1900s: Willem Einthoven developed the
modern surface electrocardiogram (ECG). Ligand-gated K⁺ 2 subunits, each with 2 homologous domains
▪ Enabled understanding of cardiac Gap Junctions
electrical potentials, their correlation with • Connexins form gap junctions: large, nonselective pores.
mechanical cardiac function, and • Allow free ion flux between adjacent myocytes.
pathophysiology of arrhythmias. • Crucial for electrical impulse propagation across the
o Mid-20th Century: myocardium.
▪ Introduction of techniques to record Ion Currents & AP Phases
cellular membrane currents. Current Type Ions Phase
▪ Surface ECG recognized as a summation
of cellular electrical activity. Inward (depolarizing) Na⁺, Ca²⁺ Phase 0
▪ Laid foundation for the development of Outward (repolarizing) K⁺ Phases 1–3
antiarrhythmic drugs. • Na⁺/Ca²⁺ channels: Open rapidly during depolarization, then
o 1960s: inactivate.
▪ First human intracardiac electrogram • K⁺ channels: Open slowly, dominate repolarization and AP
recordings. plateau.
▪ Invasive electrophysiology studies began, • Mutations in K⁺ channels cause inherited channelopathies:
primarily diagnostic. o Delayed closing = Long QT syndrome.
▪ Employed for: Regional Variations
▪ Arrhythmia mechanism
• Atria/Ventricles:
evaluation.
o Phase 0: Na⁺-driven.
▪ Antiarrhythmic drug testing.
o Phase 4: Electrically stable until next stimulus.
▪ Risk stratification of sudden
• SA/AV Nodes:
cardiac death (via
o Phase 0: Ca²⁺-driven.
programmed stimulation).
o Phase 4: Spontaneous depolarization due to
o 1960s–1970s:
"funny current" (If, Na⁺/Ca²⁺ influx).
▪ Cardiac surgery was the only invasive
treatment for arrhythmias. ▪ Targeted by ivabradine.
o 1980s:
▪ Development of radiofrequency NORMAL CARDIAC IMPULSE PROPAGATION
catheter ablation revolutionized Pathway of Normal Impulse
treatment. 1. SA node (RA-SVC junction): Initiates the impulse.
▪ Emergence of interventional o Exhibits automaticity.
electrophysiology. o Modulated by autonomic innervation.
o Late 20th Century: 2. Atria: Impulse spreads across RA and LA.
▪ Advancement of implantable devices: o Initiates atrial systole.
pacemakers and implantable 3. AV node:
cardioverter-defibrillators (ICDs). o Slower conduction.
▪ Establishment of clinical cardiac o Provides AV delay for synchrony.
electrophysiology as a distinct medical o PR interval reflects AV nodal delay.
subspecialty. 4. Bundle of His → Bundle branches:
o Right and left branches.
CELLULAR ELECTROPHYSIOLOGY o Left bundle → anterior and posterior fascicles.
Action Potential (AP) Phases in Cardiac Myocytes 5. Purkinje fibers:
o Rapid conduction (2–3 m/s).
• Phases of AP:
o Endocardial → epicardial depolarization.
o Phase 0: Rapid depolarization (Na⁺ influx) → QRS
o Enables synchronized ventricular contraction.
complex.
6. Repolarization:
o Phase 1–2: Early repolarization + plateau (Ca²⁺
o Epicardium to endocardium.
influx, K⁺ out) → ST segment.
o Explains concordance of QRS and T waves.
o Phase 3: Final repolarization (K⁺ efflux) → T
Factors Affecting Conduction Velocity
wave.
• Purkinje fibers: Faster due to specialized connexins in gap
o Phase 4: Resting potential (Na⁺/K⁺ ATPase, low
junctions.
ion flux) → interval between T and QRS.
• Myocytes: Slower conduction (0.3–0.4 m/s).
• P wave: Atrial depolarization.
• PR interval: Conduction from atrial depolarization to MECHANISMS OF CARDIAC ARRHYTHMIAS
ventricular activation (mainly AV node delay). 1. Bradyarrhythmias
Ion Channel Function and Structure
• Caused by impaired impulse generation or conduction.
• Ion flux generates the AP via electrochemical gradients.
• Common mechanisms:
• Channels are activated by: o SA node dysfunction → sinus bradycardia.
o Changes in membrane voltage (voltage-gated). o AV node block.
o Binding of ligands (ligand-gated). o His-Purkinje system disease → conduction
o Mechanical stretch (stretch-activated). block.
• Ion channel components: 2. Tachyarrhythmias
o Central pore for selective ion conductance. • Can arise from atria, ventricles, or conduction system.
o Gating apparatus for opening/inactivation.
• Mechanisms:
o Often includes auxiliary subunits for regulatory
Enhanced Automaticity
functions.
, • Abnormal spontaneous depolarization. 1. Anatomic Reentry:
• Seen in atrial, junctional, or ventricular foci. o Around fixed barrier (scar, anatomic structure).
Triggered Activity o Requires:
• Afterdepolarizations: ▪ Unidirectional block.
o Early (EADs): Phase 2–3 (e.g., long QT ▪ Slow conduction.
syndromes). ▪ Sufficient pathway length (wavelength λ =
o Delayed (DADs): Phase 4 (e.g., digoxin toxicity). θ × tr).
Reentry o Seen in:
• Circus movement of electrical impulses through pathways ▪ Atrial flutter.
with unidirectional block and slow conduction. ▪ AVNRT.
• Requires: ▪ AVRT.
o Unidirectional block ▪ Scar-related VT.
o Two pathways 2. Functional Reentry:
o Timing differences o Around area of transient refractoriness.
■■ ENHANCED AUTOMATICITY o Less stable, dynamic, polymorphic.
• Definition: Spontaneous depolarizations during phase 4 of o Underlies:
the action potential. ▪ AF.
• Normal Sites: SA node, AV node, His-Purkinje system. ▪ VF.
Predisposing Factors:
• Escape Rhythms: Emerge from distal conduction tissues if
proximal automaticity is impaired. • Ischemia/infarct: heterogeneous fibrosis, border zones.
Mechanism: • Connexin/gap junction downregulation: slows conduction.
• Driven by ionic currents: • Ion channel mutations/drugs: delayed K+ channel closing or
o SA node: If current (nonselective Na/Ca). Na+ inactivation.
o Others: K currents, Ca currents, Na/Ca
exchangers, Na/K ATPase. ■■ TREATMENT UNDERPINNINGS
Autonomic Regulation: 1. Pharmacologic:
• Parasympathetic (ACh): • Enhanced Automaticity:
o Binds IKACh channel. o β-blockers, Ca channel blockers, ivabradine.
o K+ efflux → hyperpolarization → slows phase 4 • Triggered Arrhythmias:
depolarization. o Remove offending agents (e.g., digoxin).
• Sympathetic (Catecholamines): o Normalize electrolytes.
o β-1 stimulation → L-type Ca channel activation → o Shorten QT via pacing.
increased Ca influx → enhanced phase 4 • Reentrant Arrhythmias:
depolarization → increased rate. o Increase refractory period (K channel blockers).
Intrinsic Heart Rate (IHR): o Slowing conduction (Na channel blockers) can
• Native SA node rate without autonomic input. paradoxically increase proarrhythmia if not
Abnormal Enhanced Automaticity: adequate.
• Occurs in SA, AV, His-Purkinje systems, pulmonary veins, 2. Catheter Ablation:
SVC, coronary sinus, outflow tracts. • Automaticity: Ablate focal trigger.
• Causes: • Anatomic Reentry: Target critical slow conduction pathway.
o Myocardial injury (e.g., ischemia, infarct border • Functional Reentry (e.g., AF/VF): Often less successful.
zones).
o Reperfusion injury. ■■ EVALUATION AND DIAGNOSIS
o Pulmonary vein foci: paroxysmal AF. 1. Clinical History:
o Atrial tachycardias. • Symptoms: palpitations, syncope, fatigue, chest pain,
dyspnea.
■■ AFTERDEPOLARIZATIONS AND TRIGGERED ARRHYTHMIAS • Context: activity, stress, medications, family history (SCD).
Definitions: 2. ECG:
• Abnormal depolarizations post-AP, may trigger sustained • Gold standard.
arrhythmia. • 12-lead resting ECG: look for arrhythmia, predisposing
Types: disease, inherited syndromes.
1. Early Afterdepolarizations (EADs): • Ambulatory monitoring:
o Occur in phases 2–3. o Daily: Holter.
o Associated with QT prolongation and intracellular o Intermittent: Event recorder, implantable loop
Ca overload. recorder.
o Can lead to torsades de pointes (TdP). 3. Provocative Testing:
o Causes: • Treadmill: exercise-induced arrhythmia, QT dynamics.
▪ Medications prolonging QT. • Pharmacologic: Brugada provocation.
▪ Hypokalemia, hypomagnesemia. • Carotid massage: vagal testing.
▪ Bradycardia. 4. Tilt Table Test (TTT):
▪ Electrical remodeling. • For suspected neurocardiogenic syncope.
2. Delayed Afterdepolarizations (DADs): • Now rarely used due to low sensitivity/specificity.
o Occur in phase 4. 5. Electrophysiologic Study (EPS):
o Driven by intracellular Ca overload. • Intracardiac mapping and provocation.
o Can cause repetitive depolarizations (e.g., • Confirms mechanism, helps guide ablation.
bidirectional VT). 6. Structural Imaging:
o Causes: • Echo: LV function, valve, atrial size.
▪ Digitalis toxicity.
• Cardiac CT: CAD, anatomy.
▪ Ischemia.
• MRI: Fibrosis, myocarditis, infiltrative disease.
▪ Catecholamines.
• PET: Inflammation, ischemia, sarcoidosis.
■■ REENTRY
Definition: ■■ TREATMENT
A. Antiarrhythmic Drug Therapy
• Circus movement of an electrical wavefront.
Vaughan Williams Classification:
Types:
, • Class I (Na channel blockers):
o IA: Procainamide, Quinidine.
o IB: Lidocaine, Mexiletine.
o IC: Flecainide, Propafenone.
• Class II: Beta-blockers.
• Class III (K channel blockers): Sotalol, Dofetilide, Ibutilide.
• Class IV: Verapamil, Diltiazem (L-type Ca blockers).
• Mixed actions: Amiodarone.
Challenges:
• Narrow therapeutic index.
• Significant side effects.
• Interpatient variability.
B. Catheter Ablation
• Based on localized ablation of arrhythmogenic substrate.
• Techniques:
o RF ablation (mainstay).
o Cryoablation (e.g., pulmonary veins).
o Pulsed field ablation (non-thermal electroporation).
o External beam radiotherapy (experimental).
• Mapping:
o Electroanatomic (3D mapping).
o Intracardiac echocardiography.
C. Implanted Electrical Devices
1. Pacemakers:
• Indications: Sinus node dysfunction, AV block.
• Types:
o Transvenous (leads to RA/RV).
o Leadless (RV only).
2. ICDs:
• Senses/treats VT/VF.
• Indications:
o Primary prevention (e.g., EF <35%, ischemic CM).
o Secondary prevention (survivor of SCD).
• Types:
o Transvenous.
o Subcutaneous (no transvenous leads).
, 244: THE BRADYARRYTHMIAS: DISORDERS OF THE o Fatigue, exercise intolerance, dyspnea,
SINOATRIAL NODE lightheadedness, syncope.
• Baseline ECG:
1. SA Node: Overview & Natural Pacemaker Function o May show sinus bradycardia or pauses but not
• Primary pacemaker of the heart; initiates electrical impulse always diagnostic.
that governs heart rate. • Extended monitoring:
• Located at the junction of superior vena cava and right o Holter monitor, event recorder, implantable loop
atrium on the epicardial surface (in sulcus terminalis). recorder.
o Wearables (e.g., Apple Watch) may detect
• Normal intrinsic firing rate: 60–100 bpm under
bradycardia or pauses.
parasympathetic tone.
• Exercise testing:
• Automaticity: Spontaneous depolarization via slow inward
o Standard treadmill (Bruce) may miss submaximal
currents without external stimulation.
chronotropic incompetence.
• If SA node fails, subsidiary pacemakers (AV node or
o Gradual protocols better for detecting rate
ventricular Purkinje system) take over:
abnormalities.
o Result in junctional or ventricular escape
• Exclude reversible causes:
rhythms (slower rates).
o Hypothyroidism, sleep apnea, medications (beta
blockers, digoxin, CCBs).
2. Structure and Microanatomy of the SA Node
• Imaging:
• Composed of:
o Echo: structural heart disease.
o Clusters of small fusiform pacemaker myocytes.
o MRI/CT: infiltrative diseases (amyloidosis,
o Surrounded by fibroblasts, endothelial, transitional
myocarditis).
cells.
• Electrophysiology Study (EPS):
• Central nodal cells:
o Rarely used; may assess sinus node recovery
o Poorly developed sarcoplasmic reticulum, no T-
time (SNRT) and SA conduction time (SACT).
tubules, no intercalated disks.
o Intrinsic heart rate formula: 118.1 – (0.57 × age).
o Fewer myofibrils than atrial myocardium.
o No EPS indication in asymptomatic
• Peripheral cells: Transitional phenotype between nodal and
bradycardia.
atrial cells.
• SA nodal artery: 7. Types/Subtypes of Sinus Node Dysfunction
o From right coronary artery (55–60%) or left A. Impulse Formation Abnormalities
circumflex artery (40–45%).
• Sinus Arrest:
o Enveloped by connective tissue: insulates from
o Complete failure of impulse generation.
surrounding atrial hyperpolarization.
o ECG: prolonged pause with no P waves.
B. Impulse Conduction Abnormalities (SA Exit Block)
3. Electrophysiology of SA Nodal Cells
• SA Exit Block:
• Pacemaker potential (Phase 4):
o Impulse is generated but fails to exit to atria.
o Caused by:
o Analogous to AV block; may need EPS to classify:
▪ Funny current (If) → slow inward Na⁺.
▪ Type I (Wenckebach): Progressive P-P
▪ T-type and L-type Ca²⁺ channels.
interval shortening → pause.
o Leads to automaticity (no true resting potential). ▪ Type II (Mobitz-like): Fixed or variable
• Phase 0 (upstroke): drop of sinus impulses (e.g., every other
o Mediated by slow inward Ca²⁺ currents (not Na⁺ impulse fails).
as in working myocardium). ▪ Complete SA block: no atrial activity
o Results in slower and smaller amplitude AP. seen; escape rhythms may occur.
• Phase 4 depolarization: Most rapid in SA node → dominant • ECG: Inferred from P wave abnormalities (sinus pauses,
pacemaker. dropped beats).
• No fast sodium channels → depolarization is slow. C. Tachy-Brady Syndrome
• Electrical connection to atrial myocardium via transitional • Alternation of atrial tachyarrhythmias (esp. AFib) with
cells. bradycardia or long pauses.
• Bradycardia exacerbated by rate control drugs.
4. Autonomic Regulation • Often an indication for permanent pacemaker (PPM) to
• Parasympathetic (vagal) dominance at rest slows rate. allow pharmacologic rate control.
• Sympathetic stimulation increases phase 4 slope → higher D. Chronotropic Incompetence (CI)
rate. • Inability to increase heart rate appropriately during exertion.
• Intrinsic heart rate (denervated heart): ~100–110 bpm. • Associated with exercise intolerance, poor VO₂ max, and
• SA node exhibits rate-dependent site shift: worse cardiovascular prognosis.
o Superior shift with faster rates. • Defined by:
o Inferior shift with slower rates → affects P wave o Inability to reach target HR: [208 – (0.7 × age)].
morphology. o Heart rate instability or submaximal response.
• May be missed with standard treadmill testing.
5. Age-Related Changes
• Maximum heart rate declines with age. 8. Other Causes of SA Node Dysfunction
• Resting heart rate usually preserved but parasympathetic A. SA Node Fibrosis
tone decreases. • Common in elderly due to age-related tissue changes.
• Age-associated changes: • May be asymptomatic or result in clinical
o Sinus node fibrosis. bradyarrhythmia.
o Loss of pacemaker cells. B. SA Node Ischemia/Infarction
o May lead to clinical SND in some, though many • Often seen in inferior MI (RCA involvement).
elderly maintain normal rhythm.
• May be transient, potentiated by vagal tone or drugs (beta
blockers, morphine).
6. Diagnosis of Sinus Node Dysfunction (SND)
• Rare cases may have permanent dysfunction.
• Also known as Sick Sinus Syndrome (SSS).
• Risk of SA nodal artery injury during AF ablation
• Symptoms:
procedures.
ELECTROPHYSIOLOGY amino acids).
• Selectivity: Determined by amino acid composition in the P
HISTORICAL PERSPECTIVE OF CARDIAC ELECTROPHYSIOLOGY domain.
• Definition: Clinical cardiac electrophysiology is a cardiology Types of Channel Architecture
subspecialty focused on diagnosing and managing heart Channel Type Structure
rhythm disorders (arrhythmias). Voltage-gated K⁺ 4 separate homologous α subunits
• Key Historical Milestones:
Voltage-gated Na⁺/Ca²⁺ 1 α subunit with 4 homologous domains
o Early 1900s: Willem Einthoven developed the
modern surface electrocardiogram (ECG). Ligand-gated K⁺ 2 subunits, each with 2 homologous domains
▪ Enabled understanding of cardiac Gap Junctions
electrical potentials, their correlation with • Connexins form gap junctions: large, nonselective pores.
mechanical cardiac function, and • Allow free ion flux between adjacent myocytes.
pathophysiology of arrhythmias. • Crucial for electrical impulse propagation across the
o Mid-20th Century: myocardium.
▪ Introduction of techniques to record Ion Currents & AP Phases
cellular membrane currents. Current Type Ions Phase
▪ Surface ECG recognized as a summation
of cellular electrical activity. Inward (depolarizing) Na⁺, Ca²⁺ Phase 0
▪ Laid foundation for the development of Outward (repolarizing) K⁺ Phases 1–3
antiarrhythmic drugs. • Na⁺/Ca²⁺ channels: Open rapidly during depolarization, then
o 1960s: inactivate.
▪ First human intracardiac electrogram • K⁺ channels: Open slowly, dominate repolarization and AP
recordings. plateau.
▪ Invasive electrophysiology studies began, • Mutations in K⁺ channels cause inherited channelopathies:
primarily diagnostic. o Delayed closing = Long QT syndrome.
▪ Employed for: Regional Variations
▪ Arrhythmia mechanism
• Atria/Ventricles:
evaluation.
o Phase 0: Na⁺-driven.
▪ Antiarrhythmic drug testing.
o Phase 4: Electrically stable until next stimulus.
▪ Risk stratification of sudden
• SA/AV Nodes:
cardiac death (via
o Phase 0: Ca²⁺-driven.
programmed stimulation).
o Phase 4: Spontaneous depolarization due to
o 1960s–1970s:
"funny current" (If, Na⁺/Ca²⁺ influx).
▪ Cardiac surgery was the only invasive
treatment for arrhythmias. ▪ Targeted by ivabradine.
o 1980s:
▪ Development of radiofrequency NORMAL CARDIAC IMPULSE PROPAGATION
catheter ablation revolutionized Pathway of Normal Impulse
treatment. 1. SA node (RA-SVC junction): Initiates the impulse.
▪ Emergence of interventional o Exhibits automaticity.
electrophysiology. o Modulated by autonomic innervation.
o Late 20th Century: 2. Atria: Impulse spreads across RA and LA.
▪ Advancement of implantable devices: o Initiates atrial systole.
pacemakers and implantable 3. AV node:
cardioverter-defibrillators (ICDs). o Slower conduction.
▪ Establishment of clinical cardiac o Provides AV delay for synchrony.
electrophysiology as a distinct medical o PR interval reflects AV nodal delay.
subspecialty. 4. Bundle of His → Bundle branches:
o Right and left branches.
CELLULAR ELECTROPHYSIOLOGY o Left bundle → anterior and posterior fascicles.
Action Potential (AP) Phases in Cardiac Myocytes 5. Purkinje fibers:
o Rapid conduction (2–3 m/s).
• Phases of AP:
o Endocardial → epicardial depolarization.
o Phase 0: Rapid depolarization (Na⁺ influx) → QRS
o Enables synchronized ventricular contraction.
complex.
6. Repolarization:
o Phase 1–2: Early repolarization + plateau (Ca²⁺
o Epicardium to endocardium.
influx, K⁺ out) → ST segment.
o Explains concordance of QRS and T waves.
o Phase 3: Final repolarization (K⁺ efflux) → T
Factors Affecting Conduction Velocity
wave.
• Purkinje fibers: Faster due to specialized connexins in gap
o Phase 4: Resting potential (Na⁺/K⁺ ATPase, low
junctions.
ion flux) → interval between T and QRS.
• Myocytes: Slower conduction (0.3–0.4 m/s).
• P wave: Atrial depolarization.
• PR interval: Conduction from atrial depolarization to MECHANISMS OF CARDIAC ARRHYTHMIAS
ventricular activation (mainly AV node delay). 1. Bradyarrhythmias
Ion Channel Function and Structure
• Caused by impaired impulse generation or conduction.
• Ion flux generates the AP via electrochemical gradients.
• Common mechanisms:
• Channels are activated by: o SA node dysfunction → sinus bradycardia.
o Changes in membrane voltage (voltage-gated). o AV node block.
o Binding of ligands (ligand-gated). o His-Purkinje system disease → conduction
o Mechanical stretch (stretch-activated). block.
• Ion channel components: 2. Tachyarrhythmias
o Central pore for selective ion conductance. • Can arise from atria, ventricles, or conduction system.
o Gating apparatus for opening/inactivation.
• Mechanisms:
o Often includes auxiliary subunits for regulatory
Enhanced Automaticity
functions.
, • Abnormal spontaneous depolarization. 1. Anatomic Reentry:
• Seen in atrial, junctional, or ventricular foci. o Around fixed barrier (scar, anatomic structure).
Triggered Activity o Requires:
• Afterdepolarizations: ▪ Unidirectional block.
o Early (EADs): Phase 2–3 (e.g., long QT ▪ Slow conduction.
syndromes). ▪ Sufficient pathway length (wavelength λ =
o Delayed (DADs): Phase 4 (e.g., digoxin toxicity). θ × tr).
Reentry o Seen in:
• Circus movement of electrical impulses through pathways ▪ Atrial flutter.
with unidirectional block and slow conduction. ▪ AVNRT.
• Requires: ▪ AVRT.
o Unidirectional block ▪ Scar-related VT.
o Two pathways 2. Functional Reentry:
o Timing differences o Around area of transient refractoriness.
■■ ENHANCED AUTOMATICITY o Less stable, dynamic, polymorphic.
• Definition: Spontaneous depolarizations during phase 4 of o Underlies:
the action potential. ▪ AF.
• Normal Sites: SA node, AV node, His-Purkinje system. ▪ VF.
Predisposing Factors:
• Escape Rhythms: Emerge from distal conduction tissues if
proximal automaticity is impaired. • Ischemia/infarct: heterogeneous fibrosis, border zones.
Mechanism: • Connexin/gap junction downregulation: slows conduction.
• Driven by ionic currents: • Ion channel mutations/drugs: delayed K+ channel closing or
o SA node: If current (nonselective Na/Ca). Na+ inactivation.
o Others: K currents, Ca currents, Na/Ca
exchangers, Na/K ATPase. ■■ TREATMENT UNDERPINNINGS
Autonomic Regulation: 1. Pharmacologic:
• Parasympathetic (ACh): • Enhanced Automaticity:
o Binds IKACh channel. o β-blockers, Ca channel blockers, ivabradine.
o K+ efflux → hyperpolarization → slows phase 4 • Triggered Arrhythmias:
depolarization. o Remove offending agents (e.g., digoxin).
• Sympathetic (Catecholamines): o Normalize electrolytes.
o β-1 stimulation → L-type Ca channel activation → o Shorten QT via pacing.
increased Ca influx → enhanced phase 4 • Reentrant Arrhythmias:
depolarization → increased rate. o Increase refractory period (K channel blockers).
Intrinsic Heart Rate (IHR): o Slowing conduction (Na channel blockers) can
• Native SA node rate without autonomic input. paradoxically increase proarrhythmia if not
Abnormal Enhanced Automaticity: adequate.
• Occurs in SA, AV, His-Purkinje systems, pulmonary veins, 2. Catheter Ablation:
SVC, coronary sinus, outflow tracts. • Automaticity: Ablate focal trigger.
• Causes: • Anatomic Reentry: Target critical slow conduction pathway.
o Myocardial injury (e.g., ischemia, infarct border • Functional Reentry (e.g., AF/VF): Often less successful.
zones).
o Reperfusion injury. ■■ EVALUATION AND DIAGNOSIS
o Pulmonary vein foci: paroxysmal AF. 1. Clinical History:
o Atrial tachycardias. • Symptoms: palpitations, syncope, fatigue, chest pain,
dyspnea.
■■ AFTERDEPOLARIZATIONS AND TRIGGERED ARRHYTHMIAS • Context: activity, stress, medications, family history (SCD).
Definitions: 2. ECG:
• Abnormal depolarizations post-AP, may trigger sustained • Gold standard.
arrhythmia. • 12-lead resting ECG: look for arrhythmia, predisposing
Types: disease, inherited syndromes.
1. Early Afterdepolarizations (EADs): • Ambulatory monitoring:
o Occur in phases 2–3. o Daily: Holter.
o Associated with QT prolongation and intracellular o Intermittent: Event recorder, implantable loop
Ca overload. recorder.
o Can lead to torsades de pointes (TdP). 3. Provocative Testing:
o Causes: • Treadmill: exercise-induced arrhythmia, QT dynamics.
▪ Medications prolonging QT. • Pharmacologic: Brugada provocation.
▪ Hypokalemia, hypomagnesemia. • Carotid massage: vagal testing.
▪ Bradycardia. 4. Tilt Table Test (TTT):
▪ Electrical remodeling. • For suspected neurocardiogenic syncope.
2. Delayed Afterdepolarizations (DADs): • Now rarely used due to low sensitivity/specificity.
o Occur in phase 4. 5. Electrophysiologic Study (EPS):
o Driven by intracellular Ca overload. • Intracardiac mapping and provocation.
o Can cause repetitive depolarizations (e.g., • Confirms mechanism, helps guide ablation.
bidirectional VT). 6. Structural Imaging:
o Causes: • Echo: LV function, valve, atrial size.
▪ Digitalis toxicity.
• Cardiac CT: CAD, anatomy.
▪ Ischemia.
• MRI: Fibrosis, myocarditis, infiltrative disease.
▪ Catecholamines.
• PET: Inflammation, ischemia, sarcoidosis.
■■ REENTRY
Definition: ■■ TREATMENT
A. Antiarrhythmic Drug Therapy
• Circus movement of an electrical wavefront.
Vaughan Williams Classification:
Types:
, • Class I (Na channel blockers):
o IA: Procainamide, Quinidine.
o IB: Lidocaine, Mexiletine.
o IC: Flecainide, Propafenone.
• Class II: Beta-blockers.
• Class III (K channel blockers): Sotalol, Dofetilide, Ibutilide.
• Class IV: Verapamil, Diltiazem (L-type Ca blockers).
• Mixed actions: Amiodarone.
Challenges:
• Narrow therapeutic index.
• Significant side effects.
• Interpatient variability.
B. Catheter Ablation
• Based on localized ablation of arrhythmogenic substrate.
• Techniques:
o RF ablation (mainstay).
o Cryoablation (e.g., pulmonary veins).
o Pulsed field ablation (non-thermal electroporation).
o External beam radiotherapy (experimental).
• Mapping:
o Electroanatomic (3D mapping).
o Intracardiac echocardiography.
C. Implanted Electrical Devices
1. Pacemakers:
• Indications: Sinus node dysfunction, AV block.
• Types:
o Transvenous (leads to RA/RV).
o Leadless (RV only).
2. ICDs:
• Senses/treats VT/VF.
• Indications:
o Primary prevention (e.g., EF <35%, ischemic CM).
o Secondary prevention (survivor of SCD).
• Types:
o Transvenous.
o Subcutaneous (no transvenous leads).
, 244: THE BRADYARRYTHMIAS: DISORDERS OF THE o Fatigue, exercise intolerance, dyspnea,
SINOATRIAL NODE lightheadedness, syncope.
• Baseline ECG:
1. SA Node: Overview & Natural Pacemaker Function o May show sinus bradycardia or pauses but not
• Primary pacemaker of the heart; initiates electrical impulse always diagnostic.
that governs heart rate. • Extended monitoring:
• Located at the junction of superior vena cava and right o Holter monitor, event recorder, implantable loop
atrium on the epicardial surface (in sulcus terminalis). recorder.
o Wearables (e.g., Apple Watch) may detect
• Normal intrinsic firing rate: 60–100 bpm under
bradycardia or pauses.
parasympathetic tone.
• Exercise testing:
• Automaticity: Spontaneous depolarization via slow inward
o Standard treadmill (Bruce) may miss submaximal
currents without external stimulation.
chronotropic incompetence.
• If SA node fails, subsidiary pacemakers (AV node or
o Gradual protocols better for detecting rate
ventricular Purkinje system) take over:
abnormalities.
o Result in junctional or ventricular escape
• Exclude reversible causes:
rhythms (slower rates).
o Hypothyroidism, sleep apnea, medications (beta
blockers, digoxin, CCBs).
2. Structure and Microanatomy of the SA Node
• Imaging:
• Composed of:
o Echo: structural heart disease.
o Clusters of small fusiform pacemaker myocytes.
o MRI/CT: infiltrative diseases (amyloidosis,
o Surrounded by fibroblasts, endothelial, transitional
myocarditis).
cells.
• Electrophysiology Study (EPS):
• Central nodal cells:
o Rarely used; may assess sinus node recovery
o Poorly developed sarcoplasmic reticulum, no T-
time (SNRT) and SA conduction time (SACT).
tubules, no intercalated disks.
o Intrinsic heart rate formula: 118.1 – (0.57 × age).
o Fewer myofibrils than atrial myocardium.
o No EPS indication in asymptomatic
• Peripheral cells: Transitional phenotype between nodal and
bradycardia.
atrial cells.
• SA nodal artery: 7. Types/Subtypes of Sinus Node Dysfunction
o From right coronary artery (55–60%) or left A. Impulse Formation Abnormalities
circumflex artery (40–45%).
• Sinus Arrest:
o Enveloped by connective tissue: insulates from
o Complete failure of impulse generation.
surrounding atrial hyperpolarization.
o ECG: prolonged pause with no P waves.
B. Impulse Conduction Abnormalities (SA Exit Block)
3. Electrophysiology of SA Nodal Cells
• SA Exit Block:
• Pacemaker potential (Phase 4):
o Impulse is generated but fails to exit to atria.
o Caused by:
o Analogous to AV block; may need EPS to classify:
▪ Funny current (If) → slow inward Na⁺.
▪ Type I (Wenckebach): Progressive P-P
▪ T-type and L-type Ca²⁺ channels.
interval shortening → pause.
o Leads to automaticity (no true resting potential). ▪ Type II (Mobitz-like): Fixed or variable
• Phase 0 (upstroke): drop of sinus impulses (e.g., every other
o Mediated by slow inward Ca²⁺ currents (not Na⁺ impulse fails).
as in working myocardium). ▪ Complete SA block: no atrial activity
o Results in slower and smaller amplitude AP. seen; escape rhythms may occur.
• Phase 4 depolarization: Most rapid in SA node → dominant • ECG: Inferred from P wave abnormalities (sinus pauses,
pacemaker. dropped beats).
• No fast sodium channels → depolarization is slow. C. Tachy-Brady Syndrome
• Electrical connection to atrial myocardium via transitional • Alternation of atrial tachyarrhythmias (esp. AFib) with
cells. bradycardia or long pauses.
• Bradycardia exacerbated by rate control drugs.
4. Autonomic Regulation • Often an indication for permanent pacemaker (PPM) to
• Parasympathetic (vagal) dominance at rest slows rate. allow pharmacologic rate control.
• Sympathetic stimulation increases phase 4 slope → higher D. Chronotropic Incompetence (CI)
rate. • Inability to increase heart rate appropriately during exertion.
• Intrinsic heart rate (denervated heart): ~100–110 bpm. • Associated with exercise intolerance, poor VO₂ max, and
• SA node exhibits rate-dependent site shift: worse cardiovascular prognosis.
o Superior shift with faster rates. • Defined by:
o Inferior shift with slower rates → affects P wave o Inability to reach target HR: [208 – (0.7 × age)].
morphology. o Heart rate instability or submaximal response.
• May be missed with standard treadmill testing.
5. Age-Related Changes
• Maximum heart rate declines with age. 8. Other Causes of SA Node Dysfunction
• Resting heart rate usually preserved but parasympathetic A. SA Node Fibrosis
tone decreases. • Common in elderly due to age-related tissue changes.
• Age-associated changes: • May be asymptomatic or result in clinical
o Sinus node fibrosis. bradyarrhythmia.
o Loss of pacemaker cells. B. SA Node Ischemia/Infarction
o May lead to clinical SND in some, though many • Often seen in inferior MI (RCA involvement).
elderly maintain normal rhythm.
• May be transient, potentiated by vagal tone or drugs (beta
blockers, morphine).
6. Diagnosis of Sinus Node Dysfunction (SND)
• Rare cases may have permanent dysfunction.
• Also known as Sick Sinus Syndrome (SSS).
• Risk of SA nodal artery injury during AF ablation
• Symptoms:
procedures.
