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Pathophysiology and Therapeutics of Ventricular Arrhythmias

Introduction

  • Instructor: Marcia L. Brackbill, Pharm.D., BCPS
  • Position: Professor of Pharmacy at Shenandoah University

Objectives

  • Differentiate between the ventricular arrhythmias discussed in lecture in terms of:
    • Definition
    • Prognosis
    • Etiology
  • Identify appropriate antiarrhythmic therapy for the treatment of:
    • Premature ventricular contractions (PVCs)
    • Ventricular tachycardia (VT)
    • Torsades de Pointes (TdP)
    • Ventricular fibrillation (VF)
  • List common side effects associated with the antiarrhythmic drugs discussed.
  • Recognize medications and clinical conditions that predispose patients to TdP.

Types of Ventricular Arrhythmias

  • Premature Ventricular Contractions (PVCs) and Ventricular Tachycardia (VT)
    • Monomorphic VT: can be stable (chronic) or acute
    • Pulseless VT
    • Unstable VT
    • Polymorphic VT
  • Torsades de Pointes (TdP)
  • Ventricular Fibrillation (VF)
  • Define sudden cardiac death.

Premature Ventricular Contractions (PVCs)

  • Definition:
    • Ectopic beats originating in the ventricular muscle due to spontaneous electrical firing of local tissue.
  • Most common arrhythmia, observed in:
    • Healthy individuals
    • Patients with coronary artery disease (CAD)
    • Up to 80% of patients with myocardial infarction (MI) in the peri-MI setting.
  • Symptoms: Unspecified but sourced from a link to pediatric cardiology information.

Etiology of PVCs

  • Medications that may cause PVCs:
    • Sympathomimetics: epinephrine, pseudoephedrine, phenylephrine
    • Methylxanthines: caffeine, theophylline
    • Other: digoxin, anesthetics, antiarrhythmics.
  • Clinical conditions that may cause PVCs:
    • Anemia
    • Hypoxia
    • Stress (surgery, critical illness)
    • Electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia).
  • Eliminating the precipitating factor generally resolves the PVCs and avoids the need for potentially toxic antiarrhythmic medications.

Identification of PVCs

  • Frequency of PVCs: Highly variable, making detection challenging.
  • Holter Monitor: Used for identification of arrhythmias that may not occur during standard EKGs. Also assesses:
    • Recurrent symptoms
    • Evaluates effectiveness of medication therapy.

Treatment of PVCs

  • Key Question: When can the treatment of PVCs be dangerous?
  • Specific Drugs: Identify which drugs should be avoided in specific situations involving PVCs.

Ventricular Tachycardia (VT)

  • Definition: Rapid, regular, ectopic rhythm of 3 or more PVCs; considered more serious than PVCs.
  • Mechanism: Produces hemodynamic compromise:
    • Decreased diastolic filling
    • Loss of coordinated contraction with the atria.
  • Can degenerate into ventricular fibrillation which is a major concern.

VT Terminology

  • NSVT (Non-sustained Monomorphic Ventricular Tachycardia):
    • > 3 coupled PVCs at rates > 100 beats/min terminating in < 30 seconds; generally asymptomatic; typically no drug therapy required.
  • SVT (Sustained Monomorphic VT):
    • Present for > 30 seconds; often leads to hemodynamic instability; interventions required.
  • Other VT Terminology:
    • Monomorphic: Consistent QRS morphology.
    • Polymorphic: Varying QRS complex sizes; relevant example includes Torsades de Pointes (TdP).

Monomorphic VT

Stable (Chronic) VT
  • Usually indicates underlying heart disease (e.g., idiopathic dilated cardiomyopathy).
  • High risk associated with chronic, recurrent sustained VT.
  • Management typically important due to the risk of longer episodes of NSVT (up to 30 seconds).
  • If asymptomatic, drug therapy may not be needed; if symptomatic, preventative therapies (ICDs or chronic drug therapy) are often required.
Acute VT
  • **Types: **
    • Pulseless VT (Medical emergency; no cardiac output).
    • Unstable VT (Patients are highly symptomatic).
  • Primary Treatment: Follow Acute Cardiac Life Support (ACLS) algorithm:
    • Most common causes include:
    • Ischemia/Myocardial infarction
    • Metabolic abnormalities.
  • Goals: Restore hemodynamic stability and correct underlying factors.

Treatment of Acute VT with a Pulse

  • Assess and correct underlying causative factors (e.g., MI, ischemia).
  • Severe symptoms: Synchronized DCC (Direct Current Cardioversion) needed immediately.
  • Initial mild symptoms: May treat with antiarrhythmic agent (e.g., Amiodarone as first line). DCC should be ready to administer. Understand when to use DCC.

Treatment of Acute Pulseless VT

  • **Steps: **
    1. Call code, start CPR.
    2. Administer DCC immediately.
    3. Identify and manage underlying causes (e.g., MI).
    4. After 2 minutes of CPR, check for a pulse. If none, administer Epinephrine (1 mg) and continue CPR for 2 more minutes.
    5. If rhythm remains and no pulse, Amiodarone or Lidocaine may be considered.
    6. Perform CPR and defibrillator shocks in two-minute cycles, following ACLS guidelines.

VT Review

  • Instruction: Watch a short video covering treatment of acute pulseless VT in conjunction with lecture material.

Amiodarone for Acute VT

  • Use: Best evidence-based support for shock refractory VT/VF; most effective for recurrent VT.
  • Dosage:
    • 300 mg IV bolus for VF or pulseless VT during ACLS.
    • 150 mg IV bolus over 10 minutes for VT with a pulse.
  • Adverse effects (both acute and chronic):
    • Acute: [Unspecified]
    • Chronic: CNS effects, corneal microdeposits leading to blurred vision, optic neuritis, GI issues, pulmonary fibrosis, hepatitis/hepatotoxicity, thyroid dysfunction (hypo/hyper), photosensitivity, blue-gray skin.

Lidocaine for Acute VT

  • Use: Provides rapid control of VT in acute scenarios.
  • **Administration: **
    • Bolus/loading dose followed by continuous infusion.
    • Requires maintenance infusion due to rapid distribution.
  • Considerations: Narrow therapeutic index and potential for significant neurologic side effects (e.g., paresthesia, confusion, slurred speech, etc.).

Reasons for Fewer Antiarrhythmics Being Used Chronically for VT Prevention

  1. Low likelihood of finding an effective drug.
  2. Amiodarone’s clear efficacy.
  3. High recurrence rates of life-threatening VT.
  4. Notable side effect profile of antiarrhythmics.
  5. Effectiveness of newer non-drug approaches (ICDs).

Non-Pharmacologic Therapy for VT

  • Implantable Cardio Defibrillator (ICD):
    • Early trials like MADIT showed improvement in survival; ICDs preferred over conventional antiarrhythmics.
    • Most common therapy for sustained VT/VF, though costly.
  • Up to 50% of ICD patients may still require antiarrhythmic drugs.

Proarrhythmia

  • Definition: A phenomenon where treatment results in new or worsening arrhythmias.
  • Consequences: Can range from asymptomatic to life-threatening arrhythmias (e.g., Torsades de Pointes).
  • Diagnosis Conflict: Difficult to diagnose; protocols needed if proarrhythmia is suspected.

Proarrhythmia: Torsades de Pointes (TdP)

  • Description: Caused by delayed ventricular repolarization due to potassium conductance blockade.
  • Etiologies: Various medications and conditions may predispose patients to TdP.
  • Possibly linked to hereditary syndromes with potassium channel abnormalities.

Reported Causes of Prolonged QT and TdP

  • Various physiological conditions and medications lead to QT prolongation and TdP:
    • Congenital long QT syndrome
    • Electrolyte imbalances
    • Myocardial infarction
    • Certain drugs like quinidine.
  • Research Importance: Pharmacists must be aware of causative drugs and conditions.

Treatment of TdP

  • Most patients respond to DCC; drug therapy needed to manage recurrences.
  • First-line Therapy: May cause hypotension; discontinuation of agents prolonging QT interval is crucial.

Ventricular Fibrillation (VF)

  • Definition: Characterized by electrical chaos, with disorganized rhythm (150-500 beats/min).
  • Results in randomized, independent contraction of cardiac fibers leading to loss of cardiac output.
  • Medical Emergency: Death can occur rapidly without intervention; prognosis is poor if untreated.

Treatment of VF

  • Management according to ACLS guidelines:
    • CPR and DCC shocks.
    • Administer Epinephrine if VF continues post-shock.
    • Consider antiarrhythmics post-resuscitation until patient is stabilized.
    • If VF is due to ischemia, prompt reperfusion therapy is necessitated.
    • Presence of an ICD is required if VF arises without an identifiable precipitating factor.

Case Study #1

  • Patient: DD, 42, admitted post-MI. Presenting with PVCs.
  • Clinical Question: Should DD be treated for PVCs? If yes, what options are appropriate? Should antiarrhythmics be considered?

Case Study #2

  • Patient Background: JJ, 60, presents to ER with severe symptoms indicative of VT. Relevant medical history includes:
    • Hypertension
    • BPH
    • Diabetes
    • Recent MI.
  • Clinical Concerns:
    • Determine the type of VT.
    • Importance of symptoms in therapy decision.
    • Treatment plans for JJ considering acute management.

Case Study #3

  • Continuation of Case Study for JJ:
    • Administered lidocaine but experiencing neurological side effects, suggesting adverse reactions to the drug. Considerations for long-term antiarrhythmic therapy (sotalol).
    • Monitor patient especially for potassium levels and other drug interactions (e.g., fluoroquinolones).
  • Future Monitoring: Assess for additional arrhythmias (TdP and polymorphic VT); review adverse events post-sotalol treatment.