17. Inherited Channelopathies and Primary Electrical Diseases

Channelopathies in adults require systematic risk stratification for the prevention of sudden cardiac arrest in individuals with structurally normal hearts.

Brugada Syndrome Figure 17.1: Type 1 Brugada Pattern: Coved-type ST-segment elevation >= 2 mm followed by an inverted T wave in right precordial leads V1-V2.


1. Classification of Major Channelopathies

ChannelopathyMutated Genes / ChannelsClassical 12-Lead Electrocardiographic HallmarkProvocative Testing & Diagnostic TriggersDefinitive Management
Brugada Syndrome (Type 1)$SCN5A$ ($Nav1.5$, loss-of-function in $20-30\%$).Coved-type ST elevation $\ge 2\text{ mm}$ followed by a negative T wave in $\ge 1$ right precordial lead ($V_1-V_2$ in 4th, 3rd, or 2nd intercostal space).Fever, high carbohydrate meals, psychotropic drugs, Sodium Channel Blocker Challenge (IV Ajmaline $1\text{ mg/kg}$ or Flecainide $2\text{ mg/kg}$).ICD Implantation; Quinidine ($300-600\text{ mg}$ tid); Epicardial RVOT Catheter Ablation.
Short QT Syndrome (SQTS)$KCNH2, KCNQ1, KCNJ2$ (gain-of-function $K^+$).Corrected $QTc < 330-360\text{ ms}$ with tall, narrow-based, peaked T waves; virtually absent ST segment.Short atrial/ventricular refractory periods; easily inducible VF during EPS.ICD Implantation; Quinidine (prolongs QT interval and normalizes repolarization).
Early Repolarization Syndrome (Malignant ERS)$CACNA1C, KCNJ8, SCN5A$.J-point elevation $\ge 1\text{ mm}$ with horizontal or downsloping ST segment in inferior (II, III, aVF) or lateral leads.Hypothermia, bradycardia, high vagal tone.ICD; Isoproterenol infusion for electrical storm; oral Quinidine.
Catecholaminergic Polymorphic VT (CPVT)$RyR2$ (90%), $CASQ2$ (intracellular $Ca^{2+}$ leak).Completely normal resting baseline ECG; Bidirectional VT or polymorphic VT provoked during exercise/stress.Exercise Treadmill Test (ETT) or Isoproterenol infusion reproducing bidirectional VT.Nadolol + Flecainide; Left Cardiac Sympathetic Denervation (LCSD); ICD with high-rate cutoff.

2. Emergency Management of Brugada Electrical Storm

  • IV Isoproterenol Infusion: Titrated to increase heart rate by $20\%$, increasing inward $I_{Ca,L}$ to overcome outward $I_{to}$ and aborting VF storm.
  • Oral / IV Quinidine: Blocks $I_{to}$, normalizing ST-segment elevation.