History and exam
Key diagnostic factors
common
history of known gene mutation
Includes KCNQ1 gene mutations, KCNH2 gene mutations, SCN5A gene mutations, and CALM gene mutations.
use of drugs or circumstances known to increase the QT interval
Some of the drugs known to prolong the QT interval or cause depletion of potassium and/or magnesium are quinidine, procainamide, sotalol, amiodarone, disopyramide, dofetilide, phenothiazines, tricyclic antidepressants, and methadone.[21][22] Credible Meds (Arizona CERT): drugs that prolong the QT interval Opens in new window Certain cancer treatments are also known to cause QT prolongation, e.g., kinase inhibitors, growth factor inhibitors, androgen-deprivation therapies, and chimeric antigen receptor T-cell therapies.[23][24]
Electrolyte imbalances and bradyarrhythmias may result in QT prolongation.
syncope during heightened adrenergic tones
Patients with LQT1 typically have cardiac events during exercise, particularly swimming.
syncope during arousal or surprise
Patients with LQT2 commonly have cardiac events during arousal or when startled, as by a telephone or alarm clock.
arrhythmic symptoms postpartum
Female patients with LQT2 are more prone to developing arrhythmic symptoms during the first 9 postpartum months.[35]
syncope at rest and during bradycardia
Patients with LQT3 commonly have cardiac events at rest and during bradycardia.
cardiac syncope
Normally secondary to ventricular tachyarrhythmias or bradyarrhythmias.
Characterized by premonitory symptoms such as palpitations, chest pain, and dyspnea. During the syncopal episode, pallor and cyanosis are common features, and the recovery period is brief and characterized by flushing.
Complete atrioventricular block may present with cardiac syncope.
palpitations
Congenital and acquired LQTS may present with palpitations secondary to premature ventricular complex and tachyarrhythmias including torsades de pointes.
uncommon
periodic paralysis
Patients with Andersen-Tawil syndrome have periodic paralysis (transient paralysis involving any part of the body and lasting seconds to hours, typically resolving spontaneously and sometimes associated with confusion and altered mental status).
dysmorphic features
Patients with Andersen-Tawil syndrome have a variety of dysmorphic features[10] including micrognathia, low-set ears, widely spaced eyes, clinodactyly, syndactyly, and scoliosis. The very rare Timothy syndrome (LQT8) can include dysmorphic features such as small upper jaw, low set ears, flattened nasal bridge, and cutaneous syndactyly.
sensorineural deafness
Jervell and Lange-Nielsen syndrome is a very severe form of LQTS associated with sensorineural deafness.[9]
Other diagnostic factors
common
dizziness
Consequence of poor cerebral perfusion due to reduced cardiac output in complete atrioventricular block and transient ventricular tachyarrhythmias or torsades de pointes.
uncommon
angina
Potential symptom of complete atrioventricular block.
fatigue
Fatigue, listlessness, and poor effort tolerance are symptoms of reduced cardiac output in complete atrioventricular block.
oliguria
Consequence of poor renal perfusion due to reduced cardiac output in complete atrioventricular block.
muscle weakness
Although hypokalemia is normally asymptomatic, it may cause muscle weakness if severe.
tetany
Hypocalcemia causes tetany, which manifests as carpopedal spasm.
numbness
Hypocalcemia causes numbness periorally and in the extremities.
Chvostek's sign
Twitching of facial muscles in response to tapping the facial nerve in the area of the parotid gland, elicited in hypocalcemia.
Trousseau's sign
Carpopedal spasm in response to inflation of a blood pressure (BP) cuff creating pressure in the upper limb greater than systolic BP, elicited in hypocalcemia.
cold and pale extremities
Signs of reduced cardiac output secondary to compensatory peripheral vasoconstriction may be present in complete atrioventricular block.
Extremities may be cyanosed and clammy.
hypotension
Sign of reduced cardiac output in complete atrioventricular block.
confusion
Consequence of poor cerebral perfusion due to reduced cardiac output in complete atrioventricular block.
Risk factors
strong
KCNQ1 gene mutations
LQT1 arises from mutations in the KCNQ1 gene. KCNQ1 mutations are the most commonly identified in genotyped patients. A homozygous mutation in KCNQ1 results in the autosomal recessive Jervell and Lange-Nielsen syndrome.[16]
KCNH2 gene mutations
LQT2 arises from mutations in the KCNH2 gene. KCNH2 mutations are the second most commonly identified, accounting for up to 35% to 45% of genotyped patients.[16]
SCN5A gene mutations
LQT3 arises from mutations in the SCN5A gene.[16]
QT interval-prolonging drugs
Ingestion of drugs known to prolong the QT interval is a recognized risk factor in the development of acquired LQTS, and may reveal subclinical congenital LQTS.[27]
Some of the drugs known to prolong the QT interval or cause depletion of potassium and/or magnesium include quinidine, procainamide, sotalol, amiodarone, disopyramide, dofetilide, phenothiazines, tricyclic antidepressants, and methadone.[21][22] Credible Meds (Arizona CERT): drugs that prolong the QT interval Opens in new window Certain cancer treatments are also known to cause QT prolongation, e.g., kinase inhibitors, growth factor inhibitors, androgen-deprivation therapies, and chimeric antigen receptor T-cell therapies.[23][24]
hypokalemia
Hypokalemia causes hyperpolarization of myocardial cell membranes with consequent prolongation of repolarization, thus prolonging the QT interval.
hypomagnesemia
Hypomagnesemia causes early afterdepolarizations, which in turn lead to prolonged repolarization of myocardial cells, thus prolonging the QT interval.
hypocalcemia
Hypocalcemia prolongs the plateau phase of the action potential, thereby prolonging repolarization of myocardial cells, thus prolonging the QT interval.
bradyarrhythmias
Any sudden bradycardia or atrioventricular nodal block may result in QT prolongation or pause-dependent QT prolongation.
central nervous system lesions
Lesions such as intracranial hemorrhage (especially subarachnoid hemorrhage) and ischemic strokes.
weak
female sex
LQTS is more commonly diagnosed in women, which may be a spurious observation resulting from the higher upper limit for the corrected QT interval (QTc) in postpubertal females than in males (460 ms and 450 ms, respectively), although one report suggests a slightly higher incidence in females on the basis of genetics.[15]
In early childhood, boys with LQT1 are more likely to experience syncope or sudden death, but boys are less likely than girls to have symptoms later in life.[8][28]
Women with LQT2 appear to be at higher risk of cardiac arrest, syncope, and/or sudden death than men and remain at risk into adulthood.[29][30]
Number of overall deaths is greater in women than in men.[28]
malnutrition
Starvation and a liquid protein diet are known triggers of a prolonged QT interval.
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