Prolonged QT Intervals and Cardiac Channelopathies

Overview and Pathophysiology

QT Interval

• The QT interval can be described as the time from the beginning of ventricular depolarization (Q wave on electrocardiogram [ECG]) to the end of ventricular repolarization (T wave on ECG).¹

• The QT interval can vary depending on various factors, including age, sex, and heart rate. Bradycardia prolongs the QT interval, while tachycardia shortens the QT interval.¹
• There are several formulas to correct for a QT (noted as QTc)¹:
  • Bazett: QT/RR¹
  • Fridericia: QT/RR^1,2
  • Framingham: QT + 0.154(1-RR)
  • Hodges and Colleagues: QT – 1.75(HR-60)
• The parameters of a normal, borderline, and prolonged QTc are listed in Table 1.

Causes of Prolonged QT Interval²

• Medical causes: myocardial ischemia, sinus node dysfunction, hypothyroidism, hypothermia, cocaine abuse, human immunodeficiency virus infection, intracranial diseases, etc.
• Electrolyte abnormalities: hypokalemia, hypocalcemia, and hypomagnesemia
• Drugs:
  • Antipsychotics: haloperidol, ziprasidone, quetiapine, thioridazine, olanzapine, risperidone
  • Antiarrhythmics: amiodarone, sotalol, dofetilide, procainamide, quinidine, flecainide
  • Antibiotics: macrolides, fluoroquinolones
  • Antidepressants: amitriptyline, imipramine, citalopram, amitriptyline
  • Antiemetics: droperidol, 5-HT₃ antagonists (ondansetron, dolasetron, granisetron), metoclopramide
  • Inhaled anesthetics: sevoflurane
  • Diuretics: furosemide, hydrochlorthiazide
  • Others: methadone, sumatriptan, cisapride³

Torsades de Pointes

• A prolonged QT can increase the risk of torsades de pointes, a polymorphic ventricular tachycardia noted for its twisting QRS complexes of varying magnitude on ECG. Torsades can be life-threatening and can lead to complications such as syncope, seizures, or even sudden cardiac death if not managed appropriately.³

• Management of Torsades de Pointes²
  • Prevent initial onset by avoiding QT prolonging drugs if possible and correcting electrolyte abnormalities.
  • When torsades occurs, most episodes are self-limiting. However, there is a risk of the patient developing ventricular fibrillation.
  • Magnesium (slow 2 g IV push with an infusion of 1 gm to 4 gm / hour until serum levels greater than 2 mmol/L) should be administered as soon as possible to stabilize the cardiac membrane.
  • Synchronized electrical cardioversion should be performed on patients who are hemodynamically unstable.
  • Pulseless patients should be defibrillated.
  • Another option for torsades is overdrive pacing to increase the heart rate.

Cardiac Channelopathies

Channelopathies

• Cardiac channelopathies are a group of genetic or acquired disorders that involve the dysfunction of myocardial ion channels such as potassium, sodium, and calcium.³
• These channelopathies lead to altered permeabilities of ion channels, which lead to³:
  • Proarrhythmic ECG changes and sudden unexplained cardiac death.
  • Delayed ventricular repolarization.
  • Prolonged QT → torsades de pointes
  • Heterogenous depolarization
• Cardiac channelopathies can be subcategorized into the following:
  • Congenital long QT syndrome (c-LQTS)
  • Brugada syndrome
  • Catecholaminergic polymorphic ventricular tachycardia
  • Sick sinus syndrome (SSS)
  • Short QT syndrome (SQTS)
  • Cardiac conduction disease (CCD)
  • Familial atrial fibrillation

Congenital Long QT Syndrome

• Long QT syndrome is an inherited (c-LQTS) or acquired disorder of cardiac ion channels that impacts cellular repolarization and results in tachyarrhythmias due to a prolonged QT interval.³
• Multiple genes, loci, proteins, and ion channels can be at fault for congenital long QT, with the most commonly affecting genes being KCNQ1, KCNH2, and SCN5A.⁴
• The major c-LQTSs are Romano Ward syndrome (autosomal dominant with normal hearing) and Jervell and Lange-Nielsen syndrome (autosomal recessive with associated sensorineural hearing loss).⁴
• The administration of IV magnesium sulfate infusion is key to preventing the occurrence of torsades de pointes in patients with c-LQTS.⁴

Brugada Syndrome

• Brugada syndrome is an inherited disorder (usually in the SCN5A gene) characterized by right ventricular conduction delay and right-sided ST changes.⁵
• Identified by ST segment elevations in leads V1-V3 and a pseudo right bundle branch block (Figure 3).⁵
• Brugada syndrome predisposes to ventricular arrhythmias, predominantly ventricular fibrillation, as opposed to torsades de pointes from ^c-LQTS.5
• The ECG changes of Brugada can be reversed with the administration of isoproterenol.³

Catecholaminergic Polymorphic Ventricular Tachycardia

• A rare hereditary disease characterized by adrenergic-dependent arrhythmias that can be lethal.
• Often, there is a family history of syncope or sudden death in 30% of affected patients.⁶
• Often diagnosed by ECG changes during exercise.
• Therapy consists of β-blockers and the placement of an implantable cardiac defibrillator.

Sick Sinus Syndrome

• A collection of disorders due to sinus node dysfunction and the inability of the heart to perform adequate pace-making and sinus rhythm. SSS can be due to a channelopathy, degenerative fibrosis, or secondary to medications or metabolic abnormalities.⁷
• Commonly seen in older patients, SSS can present as bradycardia, with some patients experiencing an accompanying tachycardia (known as tachy-brady syndrome).⁷
• As the disease progresses, symptoms begin to become more notable due to cerebral and other end-organ hypoperfusion.⁷
• Although not curable, the insertion of a pacemaker can help to manage symptoms and improve quality of life.⁷

Short QT Syndrome

• Similarly to long QT syndrome, SQTS is a rare inheritable channelopathy.⁸
• SQTS is comprises accelerated cardiac repolarization that leads to the development of life-threatening arrhythmias.⁸ 
• Patients with SQTS may experience cardiac arrest from the early neonatal period or not until the age of 80.⁸
• The main genes affected are KCNH2, KCNQ1, KCNJ2, CACNA1C, and CACNB2, which impact the transcription of L-type calcium or potassium channels.⁸
• Implantable cardioverter-defibrillators or quinidine can be used to manage arrhythmias and prolong QT interval.⁸

Cardiac Conduction Disease

• A group of diseases that impact the heart’s electrical conduction system including the sinoatrial node, atrioventricular node, Bundle of His, Purkinje fibers, or bundle branches.⁹
• CCD can lead to heart block, conduction block, or other cardiac delays, manifesting as bradycardia, syncope, and sudden cardiac death.⁹
• In addition to inherited causes (such as the SCN5A gene), CCD can be caused by degenerative conditions, ischemia, infiltrative diseases, or inflammatory conditions.⁹
• Treatment includes pacemaker implantation for patients with symptomatic bradycardia or high-degree heart block.⁹

Familial Atrial Fibrillation

• An inherited form of atrial fibrillation that has similar uncoordinated electrical activity in the atria leads to a rapid irregularly irregular heartbeat that leads to indiscernible p-waves on ECG. This can lead to embolus formation in the atrial appendage and result in stroke/sudden death.¹⁰
• Familial atrial fibrillation is an autosomal dominant condition that involves the SCN5A, KCNQ1, KCNJ2, KCNH2, and MYL4 genes.¹⁰
• While diagnostic ECG and physical findings are like nonfamilial atrial fibrillation, the combination of family history, clinical evaluation, and genetic testing can help identify familial atrial fibrillation.¹⁰
• Management is the same as general atrial fibrillation, with rate/rhythm control in combination with possible anticoagulation.¹⁰

Anesthetic Considerations in Patients with Cardiac Channelopathies

• Patients with inherited cardiac channel disorders are at high risk for perioperative arrhythmias.³
• Anesthetic management includes preoperative anxiolysis, maintaining stable hemodynamics, providing adequate anesthesia and analgesia, and maintaining normocarbia, normothermia, and normovolemia.³
• In c-LQTS, a magnesium sulfate bolus (30 mg/kg iv) and infusion should be administered to prevent torsades de pointes.³
• Drugs such as droperidol, ketamine, succinylcholine, and ondansetron should be avoided.³
  β-blocker therapy should be maintained. Propofol is a suitable anesthetic agent; fentanyl and dexmedetomidine are good choices, and inhalational agents should be used cautiously.³
• In Brugada syndrome, avoid β-blockers, α-blockers, and cholinergic drugs. Isoproterenol should be available for any ECG changes.³ Propofol and volatile anesthetics have been safely used.
• In catecholaminergic polymorphic ventricular tachycardia, β-blockers should be continued and β-agonists should be avoided, such as isoproterenol. Remifentanil is a good analgesic. Intraoperative tachycardia should be treated with a β-blocker such as esmolol or labetalol. Postoperative nausea and vomiting should be avoided; the stress can invoke arrhythmias.³