QT prolongation

Background

• Prolonged ventricular repolarization → increased risk of ventricular arrhythmias
  • Males >440-450 ms
  • Females >500 ms
  • Rule of thumb: Normal QT interval is less than half of preceding RR interval
• QT interval is from the beginning of the Q wave to the end of the T wave
  • Rate dependent and should become proportionately shorter with increasing heart rate

List of Drugs Causing QT Prolongation

• Antiarrhythmics
  • Amiodarone, disopyramide, dofetilide, flecainide, ibutilide, mexiletine, procainamide, quinidine, sotalol
• Antibiotics
  • Macrolide
    • Azithromycin, erythromycin, clarithromycin
  • Fluoroquinolone
    • Ciprofloxacin, gatifloxacin (most common), gemifloxacin, levofloxacin, moxifloxacin, ofloxacin
  • Other
    • Pentamidine, telithromycin, trimethoprim-sulfamethoxazole
• Antidepressants
  • Amitriptyline, citalopram, doxepin, fluoxetine, nortriptyline, paroxetine, sertraline, venlafaxine
• Antiemetics
  • Dolasetron, droperidol, granisetron, ondansetron
• Antifungals
  • Fluconazole, itraconazole, ketoconazole, voriconazole
• Antihypertensives
  • Nicardipine
• Antineoplastics
  • Lapatinib, nilotinib, sunitinib, tamoxifen
• Antimalarials
  • Chloroquine, halofantrine
• Antipsychotics
  • Chlorpromazine, clozapine, galantamine, haloperidol, lithium, paliperidone, pimozide, quetiapine, risperidone, thioridazine, ziprasidone
• Antivirals
  • Amantadine, atazanavir, foscarnet
• Diuretics
  • Indapamide
• Immune suppressants
  • Tacrolimus
• Opiates
  • Methadone
• Phosphodiesterase inhibitors
  • Sildenafil, Vardenafil
• Skeletal muscle relaxants
  • Tizanidine
• Urinary antispasmodics
  • Solifenacin

Clinical Features

• Most are asymptomatic
• History may include:
  • Syncope
  • Cardiac arrest
  • Family history of long QT or sudden death
• Medication history may include QT prolonging medications

Differential Diagnosis

Syncope Causes

• Cardiovascular-mediated syncope
  • Dysrhythmias:
    • WPW (pre-excitation)
    • Long QT Syndrome/QT prolongation
    • Brugada Syndrome
    • Catecholaminergic polymorphic ventricular tachycardia
    • 2nd/3rd AV Block
    • Afib/aflutter
    • Vtach/torsades
    • Sick sinus syndrome
    • Arrhythmogenic right ventricular dysplasia
    • Short QT syndrome
  • Cardiovascular disease
    • Valvular Disease (AS, MS, tricuspid stenosis)
    • Aortic Dissection
    • Myocardial Infarction
    • CHF
    • Hypertrophic Cardiomyopathy
    • PE
    • Pericardial Tamponade
    • Myxoma
    • Pulmonary Hypertension
    • Pacemaker malfunction
• Neurally mediated syncope
  • Vasovagal:
    • Fear, pain, emotion, valsalva, breath-holding spell
  • Situational (associated with):
    • Coughing, micturition, defecation, vomiting, swallowing, postexercise
    • Carotid sinus stimulation
• Orthostatic hypotension-mediated syncope:
  • Volume depletion:
    • Dehydration (vomiting, diarrhea)
    • Hemorrhage, (Ectopic Pregnancy, Upper GI Bleed/Lower GI Bleeding, Abdominal Aortic Aneurysm)
    • Sepsis
  • Autonomic Dysreflexia
  • Autonomic failure due to meds
• Other serious causes
  • Stroke
  • SAH
  • TIA
  • Vertebrobasilar Insufficiency
  • Subclavian steal
  • Heat syncope
  • Hypoglycemia
  • Hyperventilation
  • Asphyxiation
  • Seizure
  • Narcolepsy
  • Psychogenic (anxiety, conversion disorder, somatic symptom disorder)
  • Toxic (drugs, carbon monoxide, etc.)

Evaluation

Workup

• ECG
• CBC
• Chem 10

Diagnosis

Acquired QT prolongation

• ECG
  • On visual inspection, QT takes up more than half the R-R distance
  • Measure QT interval in lead II or V5-6
  • QTc = QT /√R-R

Determining Cause

• Pause Dependent (Acquired)
  • Drug induced (see drug list above)
    • Antiarrhythmics
    • Phenothiazines
    • TCAs
    • Organophosphates
    • Antihistamines
  • Electrolyte Abnormalities (hypoKalemia, hypoMag, hypoCa)
    • Hypokalemia triad
      • Long QT, ST depressions, PVCs
  • Hypothermia
  • Diet related (starvation, low protein)
  • Severe Bradycardia/AV Block
  • Hypothyroid
  • Contrast injection
  • CVA (intraparenchymal)
  • Elevated intracranial pressure and Intracranial hemorrhage
  • MI
• Adrenergic Dependent
  • Congenital
    • Jarvel/Lange-Nielsen
      • (+deafness; AR)
    • Romano-Ward syndrome
      • (normal hearing; AD)
    • Sporadic
    • Mitral valve prolapse
  • Acquired
    • CVA (subarachnoid)
    • Autonomic surgery (catechol excess: neck dissection, carotid endarterectomy, truncal vagotomy)

Management

Pause Dependent (precipitated by bradycardia)

• Unstable/sustained torsades→ defibrilation (unsynchronized)
• Stable
  • Treat underlying etiology
  • Increase HR >80 (isoproterenol or overdrive pacing)
  • Magnesium sulfate IV
  • Consider lidocaine, transvenous pacing

Adrenergic Dependent (precipited by tachycardia)

• Unstable/sustained torsades→ defibrilation (unsynchronized)
• Stable
  • Slow HR (beta-blockers)
  • May consider magnesium sulfate

Disposition

• Consider admission, especially for QT >500 or if symptomatic
• May require consultation for discontinuation of QT prolonging medications
• Avoid prescribing medications that may contribute to prolonged QT

See Also

• ECG (Main)
• Torsades de Pointes
• Hypomagnesemia
• Hypermagnesemia

Calculators

Corrected QT Interval (QTc)

Corrected QT Interval (QTc)

Parameter	Value
QT Interval (ms)
Heart Rate (bpm)
RR Interval (ms) — auto-calculated from HR	ms
Results
QTc (Bazett's) — QT / √(RR in sec)	ms
QTc (Fridericia) — QT / ∛(RR in sec)	ms

Interpretation (Bazett's QTc)
<440 ms	Normal QTc for males.
<460 ms	Normal QTc for females.
440–500 ms	Borderline/Prolonged — Monitor closely. Review medications for QT-prolonging drugs.
>500 ms	Significantly prolonged — High risk for Torsades de Pointes. Discontinue offending agents. Check Mg²⁺/K⁺/Ca²⁺.

References
Bazett HC. An analysis of the time-relations of electrocardiograms. Heart. 1920;7:353-370. Fridericia LS. Duration of systole in electrocardiogram. Acta Med Scand. 1920;53:469-486. Viskin S. Long QT syndromes and torsade de pointes. Lancet. 1999;354:1625-1633. PMID 10560690.

External Links

• Amal Mattu's Case of the Week (5/20/2012)
• Amal Mattu's Case of the Week (10/13/2014)