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Polymorphic VentricularTachycardia and Ventricular Fibrillation

Chapter 262 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 262

Key Clinical Points

  1. Polymorphic VT is characterized by a continuously changing QRS configuration from beat to beat, indicating a varying ventricular activation sequence.
  2. Torsades de pointes (TdP) is a specific form of polymorphic VT associated with QT prolongation and often triggered by a pause-dependent PVC.
  3. Congenital LQTS is categorized into three types based on genetic mutations: LQTS-1 (KCNQ1), LQTS-2 (KCNH2), and LQTS-3 (SCN5A).
  4. Brugada syndrome requires >0.2 mV of ST-segment elevation with a coved ST segment and negative T wave in more than one anterior precordial lead (V1–V3).
  5. Catecholaminergic Polymorphic VT (CPVT) is often associated with bidirectional VT or alternating QRS morphology, resulting from mutations in the ryanodine receptor or calsequestrin 2.
  6. Magnesium sulfate (1–10 mg/kg or 1–2 g IV) is the first-line treatment for Torsades de pointes; if ineffective, isoproterenol or pacing to 100–120 depolarizations/min is used.
  7. ICDs are indicated for patients with prior cardiac arrest, sustained VT, or high-risk features (e.g., LV EF <35%).
  8. Brugada syndrome involves a risk of arrhythmias associated with J-point elevation; sodium channel–blocking drugs (flecainide, ajmaline, procainamide) can unmask the condition.
  9. J-point elevation is common in patients without arrhythmias; its clinical relevance is unknown in the absence of specific symptoms.
  10. The website crediblemeds.org is a primary resource for identifying QT-prolonging medications.

1. DEFINITION & OVERVIEW

• Polymorphic Ventricular Tachycardia (VT): A form of sustained VT with a continuously changing QRS configuration from beat to beat, indicating a continually changing ventricular activation sequence. ◦ Mechanism: Unlike monomorphic VT, it does not necessarily indicate a fixed structural abnormality or focus of automaticity. ◦ Potential Mechanisms: → Variable reentrant paths → Spiral wave reentry → Multiple automatic foci → Abnormal transmural dispersion of repurpolarization (common in channelopathies or drug-induced states). ◦ Clinical Progression: Sustained polymorphic VT usually degenerates into ventricular fibrillation (VF). • Classification by Etiology/Morphology: ◦ Associated with acute myocardial infarction (MI) or ischemia. ◦ Associated with repolarization abnormalities and genetic arrhythmia syndromes (Long QT Syndrome, Brugada Syndrome). ◦ Associated with early repolarization syndrome. ◦ Associated with catecholaminergic polymorphic VT. ◦ Associated with hypertrophic cardiomyopathy (HCM). ◦ Associated with genetic dilated cardiomyopathies. ◦ Ventricular fibrillation (VF).

2. EPIDEMIOLOGY

• General: Polymorphic VT and VF are significant causes of morbidity and mortality, particularly in the setting of structural heart disease. • Dilated Cardiomyopathy: Genetic dilated cardiomyopathies account for 30–40% of cases of nonischemic dilated cardiomyopathies. • Hypertrophic Cardiomyopathy (HCM): Most common genetic cardiovascular disorder; occurs in 1 in 500 individuals; a prominent cause of sudden death before the age of 35 years. • Brugada Syndrome: Characterized as a rare syndrome. • Short QT Syndrome: Very rare compared to LQTS.

3. ETIOLOGY & PATHOPHYYSICOLOGY

• General Pathophysiology: Polymorphic VT is typically seen in association with acute MI or ischemia, ventricular hypertrophy, and genetic mutations affecting cardiac ion channels. ◦ Brugada Syndrome Mechanism: → Related to the dispersion of repolarization across the ventricular wall (epicardial and M cells are more affected than endocardial cells). → The coved ST segment in anterior precordial leads results from differences in transmembrane action potentials localized to the right ventricular outflow tract. → Genetic factors: Mutations in SCN5A, SCN1B, and SCN10A (~25% of cases); also involves calcium (loss-of-function) and potassium (gain-of-function in I_{to}) mutations. • Congenital Long QT Syndrome (LQTS): ◦ Caused by mutations in genes coding for cardiac ion channels responsible for ventricular repolarization. ◦ QTc Thresholds: >440 ms (men) and >460 ms (women). ◦ LQTS-1: Mutation in KCNQ1 gene → Reduced repolarizing current I_{Ks}. ◦ LQ2: Mutation in KCNH2 gene → Reduced repolarizing current I_{Kr}. ◦ LQTS-3: Mutation in SCN5A gene → Delayed inactivation of I_{Na}. • Catecholaminergic Polymorphic VT: ◦ Due to mutations in the cardiac ryanodine receptor or, less commonly, calsequestrin 2. ◦ Results in abnormal sarcoplasmic calcium handling. ◦ Presents as polymorphic or bidirectional VT (alternating QRS morphology). • Early Repolarization Syndrome: ◦ Characterized by J-point elevation with notching in the terminal QRS. ◦ J-point elevation is also seen in some patients with Brugada syndrome and is associated with a higher risk of arrhythmias.

4. CLINICAL FEATURES

• Symptoms and Signs: ◦ Syncope, near-syncope, or cardiac arrest. ◦ Palpitations (exercise or emotion-induced in catecholaminergic polymorphic VT). ◦ Sustained episodes degenerate to VF requiring defibrillation. • ECG Findings: ◦ Polymorphic VT: Continuously changing QRS configuration from beat to beat. ◦ Torsades de pointes: Associated with QTc >440 ms (men) or >460 ms (women). ◦ Brugada Syndrome: >0.2 mV of ST-segment elevation with a coved ST segment and negative T wave in more than one anterior precordial lead (V1–V3). ◦ Early Repolarization: J-point elevation with notching in the terminal QRS.

5. DIFFERENTIAL DIAGNOSIS

• Monomorphic VT: Fixed structural abnormality or focus of automaticity. ● Ventricular fibrillation: Disordered electrical ventricular activation without identifiable QRS complexes. ● Early repolarization syndrome: J-point elevation with notching. ● Brugada pattern (asymptomatic): Distinguished from Brugada syndrome. ● Other conditions: → Stress cardiomyopathy. → Arrhythmogenic right ventricular cardiomyopathy. → LV hypertrophy, pericarditis, myocardial ischemia/MI, hyperkalemia, hypothermia, RBBB.

6. INVESTIGATIONS & DIAGNOSIS

• Diagnostic Approach: 1. ECG Analysis: Identify QRS morphology and determine if VT is monomorphic or polymorphic. 2. Criteria Evaluation: ◦ LQTS: QTc >440 ms (men) or >460 ms (women). ◦ Brugada Syndrome: >0.2 mV ST-segment elevation with a coved ST segment and negative T wave in V1–V3. ◦ Early Repolarization: J-point elevation with notching. 3. Provocative Testing: Administration of sodium channel–blocking drugs (flecainide, ajmaline, or procainamide) can unmask ST elevation in Brugada syndrome. 4. Clinical Correlation: Use crediblemeds.org to identify QT-prolonging medications. • Causes of QT Prolongation (Table 262-1): ◦ Congenital LQTS: Types 1, 2, and 3 account for 80–90% of cases. ◦ Electrolyte Abnormalities: Hypokalemia, hypomagnesemia, hypocalcemia. ◦ Drug-induced: → Antiarrhythmics (Class IA: Quinidine, disopyramide, procainamide; Class III: Sotalol, dronedarone, ranolazine, amiodarone, ibutilide, dofetilide). → Antibiotics (Macrolides, Fluoroquinolones, Trimethoprim-sulfamethoxazole, Clindamycin, Pentamidine, Chloroquine). → Antifungals (Ketoconazole, itraconazole). → Antivirals (Amantadine). → Antipsychotics (Haloperidol, phenothiazines, thioridiazine, trifluoperazine, sertindole, zimelidine, ziprasidone). → Tricyclic and tetracyclic antidepressants. → Antihistamines (Astemizole, diphenhydramine, hydroxyzine). → Others (Citrate, Cocaine, Methadone, Hydroxychloroquine). ◦ Cardiac Conditions: Myocardial ischemia/infarction, Myocarditis, Marked bradycardia, Stress cardiomyopathy. ◦ Endocrine Disorders: Hypothyroidism, Hyperparathyroidism, Pheochromocytoma, Hyperaldosteronism. ◦ Intracranial Disorders: Subarachnoid hemorrhage, Thalamic hematoma, Cerebrovascular accident, Encephalitis, Head injury. ◦ Nutritional Disorders: Anorexia nervosa, Starvation, Liquid protein diets, Gastroplasty/ileojejunal bypass, Celiac disease.

7. MANAGEMENT & TREATMENT

  1. Acute Management: ◦ Defibrillation: Follow ACLS guidelines for sustained VT or VF. ◦ Myocardial Infarction Context: If associated with acute MI, initiate standard management: β-adrenergic blockers, electrolyte correction, and prompt myocardial reperfusion. ◦ Torsades de pointes (TdP): → First-line: Magnesium sulfate (1–2 g IV). → Second-line (if magnesium fails): Increase heart rate with isoproterenol infusion or pacing to 100–120 depolarizations/min. ◦ Supportive Care: Correct hypokalemia, hypocalcemia, and bradycardia; remove any causative QT-prolonging drugs.
  2. Long-term Management: ◦ ICD Placement: Indicated for patients with prior cardiac arrest, sustained VT, or high-risk features (e.g., LV EF <35%). ◦ Pharmacotherapy: ◦ LQTS-1/LQTS-2: Beta-blocker therapy (nadolol and propranolol are favored). ◦ General: Avoid all medications known to prolong the QT interval for patients with LQTS. ◦ Interventional Procedures: ◦ Catheter ablation: Recommended for symptomatic VT in whom medications are ineffective or not preferred.

8. PROGNOSIS & COMPLICATIONS

• Acute MI Context: Repeated episodes of polymorphic VT may suggest ongoing MI and warrant assessment of adequacy of myocardial reperfusion. • Risk Markers for Arrhythmia: ◦ QTc interval (prolonged). ◦ Bradycardia. ◦ Presence of underlying structural heart disease.

9. SPECIAL CONSIDERATIONS

• Catecholaminergic Polymorphic VT: Typically presents during childhood with exercise or emotion-induced palpitations, syncope, or cardiac arrest.

10. KEY PEARLS & CLINICAL TRAPS

• Torsades Management: Magnesium 1–2 g IV is the primary intervention for TdP; isoproterenol/pacing are used to suppress PVCs and allow time for electrolyte correction. ● Brugada Identification: Distinguish Brugada syndrome from asymptomatic patterns; use flecainide, ajmaline, or procainamide to unmask ST elevation if needed. ● J-point Distinction: J-point elevation is a common normal variant; its clinical relevance is only established in the presence of specific symptoms/arrhythmias. ● LQTS Triggers: LQTS-1 (exertion), LQTS-2 (auditory/emotional), LQTS-3 (sleep). ● Drug Safety: Use crediblemeds.org to identify QT-prolonging medications.

Reference Tables

TABLE 262-1 Causes of QT Prolongation and Torsades des Pointes 1. Congenital long QT syndromes

Harrison's 22e, p.1970

    1. Congenital long QT syndromes
      Long QT syndrome type 1: Reduced repolarizing current I due to mutation in
      Ks
      KCNQ1 gene
      Long QT syndrome type 2: Reduced repolarizing current I due to mutation in
      Kr
      KCNH2 gene
      Long QT syndrome type 3: Delayed inactivation of the I due to mutations in
      Na
      SCN5A gene
      Others: Several other types of long QT syndromes have been described; long
      QT syndrome types 1, 2, and 3 account for 80–90% of cases
      2. Electrolyte abnormalities: Hypokalemia, hypomagnesemia, hypocalcemia
      3. Drug-induced acquired prolongation of QT interval
      Antiarrhythmic drugs
      Class IA: Quinidine, disopyramide, procainamide
      Class III: Sotalol, dronedarone, ranolazine, amiodarone, ibutilide, dofetilide
      Antibiotics
      Macrolides: Erythromycin, clarithromycin, azithromycin
      Fluroquinolones: Levofloxacin, moxifloxacin
      Trimethoprim-sulfamethoxazole
      Clindamycin
      Pentamidine
      Chloroquine
      Antifungals: Ketoconazole, itraconazole
      Antivirals: Amantadine
      Antipsychotics
      Haloperidol, phenothiazines, thioridazine, trifluoperazine, sertindole,
      zimelidine, ziprasidone
      Tricyclic and tetracyclic antidepressants
      Antihistamines (histamine 1-receptor antagonists)
      Astemizole, diphenhydramine, hydroxyzine
      Other drugs
      Citrate (massive blood transfusions)
      Cocaine
      Methadone
      Hydroxychloroquine
      4. Cardiac conditions
      Myocardial ischemia and infarction
      Myocarditis
      Marked bradycardia
      Stress cardiomyopathy
      5. Endocrine disorders
      Hypothyroidism
      Hyperparathyroidism
      Pheochromocytoma
      Hyperaldosteronism
      6. Intracranial disorders
      Subarachnoid hemorrhage
      Thalamic hematoma
      Cerebrovascular accident
      Encephalitis
      Head injury
      7. Nutritional disorders
      Anorexia nervosa
      Starvation
      Liquid protein diets
      Gastroplasty and ileojejunal bypass
      Celiac disease