Diagnosis & Evaluation

Selecting Patients for Evaluation of Long QT Syndrome

Patients with a family history that reveals sudden death in young relatives or a history of syncope or seizures associated with exercise or emotional stress should be carefully evaluated for long QT syndrome (LQTS) by a cardiac specialist. Patients who develop syncope or ventricular tachycardia during or immediately after exercise should also be evaluated for LQTS. An evaluation including an ECG is especially indicated for individuals with polymorphic ventricular tachycardia or torsades de pointes — a rare ventricular arrhythmia characterized by a twisting appearance of the QRS complex — or in those with syncope associated with physical or emotional stress. Once a positive diagnosis of LQTS is made in a family, all family members, including first- and second-degree relatives, should be evaluated.

A genetic test is considered the "gold standard" for the diagnosis of LQTS but the test currently provides a definitive diagnosis in only 70 to 75 percent of patients with suspected LQTS. Until a more sensitive diagnostic test is available, clinicians often have to make diagnoses based on clinical information. This process can sometimes result in uncertainty about the definitive presence or absence of LQTS. Decisions regarding the best individual treatment plan should be made for each patient by their personal physician.

General Diagnostic Criteria

The criteria considered in the diagnosis of LQTS include measuring the patient's rate-corrected QT interval (QTc) on an electrocardiogram (ECG) and carefully determining the history for syncope, seizures, and arrhythmias in patients and their families.

The Schwartz Diagnostic Criteria in the table below provide diagnostic guidelines and suggest a scale for identifying patients with a low, intermediate, or high likelihood of having LQTS (Schwartz, 1993).

Schwartz Diagnostic Criteria for Long QT Syndrome

ECG Findings (QTc) Points
≥ 480 milliseconds 3
460 to 470 milliseconds 2
450 to 460 milliseconds (in males) 1
ECG Findings, Other Points
Torsades de pointes 2
T wave alternans 1
Notched T wave in three leads 1
Low heart rate for age 0.5
Clinical History Points
Syncope with stress 2
Syncope without stress 1
Congenital deafness 0.5
Family History Points
Family members with definite LQTS 1
Unexplained sudden cardiac death below age 30 among immediate family members 0.5
Scoring the Probability of LQTS (total of above scores) Points
Low 1
Intermediate 2 to 3
High 4

Diagnosing Long QT Syndrome

Any evaluation of a patient for an LQTS diagnosis should include:

History and ECG

Secondary Tests

If the diagnosis is unclear, or if any of the results above indicate a possible diagnosis of LQTS, the evaluation should also include:

  • Exercise stress testing by 4 or 5 years of age to measure rate-corrected QT (QTc) intervals, especially in the recovery period after exercise, and to see if ventricular arrhythmias such as polymorphic ventricular tachycardia (VT) occur
  • 24-hour Holter (ambulatory) monitoring
  • Genetic testing
  • Consideration of provocative tests such as epinephrine infusion when diagnosis is still in question

Exercise Stress Test

Exercise generally obliterates sinus arrhythmia and provides the opportunity for an ECG recording that allows a reliable QTc calculation to be made . The recovery period during which heart rates are around 120 to 130 beats per minute (bpm) generally demonstrates the greatest degree of QTc prolongation in many patients, especially those with the long QT syndrome (LQT1) subtype of LQTS. Exercise may also uncover abnormal T waves, polymorphic premature ventricular contractions (PVCs), or VT.

24-hour Ambulatory Monitor (Holter Monitor)

The 24-hour Holter monitor may be helpful in illustrating T wave abnormalities, R on T phenomenon, short runs of nonsustained VT, sustained VT, or torsades de pointes, in addition to identifying QT interval prolongation. However, a QTc interval measurement on a Holter monitor is not as helpful as the same measurement on a standard ECG. Normal QTc intervals are longer on Holter monitors than they are on standard resting ECGs, a difference that is related to differences in the equipment's filters. QTc intervals from a Holter monitor of greater than 500 milliseconds are considered abnormal, although some intervals between 470 and 500 milliseconds may be abnormal as well.

Provocative Tests

Because of the functional channel abnormalities in LQT1, most individuals with this LQTS subtype show paradoxical prolongation of the QT interval with infusion of epinephrine. This attribute can serve to unmask latent carriers of the LQT1 gene mutations.

Differential Diagnosis of LQTS

The differential diagnosis of LQTS includes conditions that lead to syncope and causes of prolonged QT intervals. The following is a list that should be considered when diagnosing LQTS:

Conditions Responsible for Syncope

  • Seizure disorders
  • Breath holding spells
  • Structural cardiac defects
  • Cardiac arrhythmias
  • Neurally-mediated syncope
  • Neurologic causes, particularly seizures
  • Metabolic causes, especially hypoglycemia
  • Emotional or psychological responses, especially conversion reactions, associated with psychogenic syncope

Factors Associated With Prolonged QT Intervals

Drugs and Medications

A variety of drugs affect ion channels and thus influence the QT interval and may be especially problematic in individuals with major LQTS mutations or other genetic variations, such as some single nucleotide polymorphisms, that may affect ion channel functioni, especially in the presence of other drugs. The following is a non-inclusive list of drugs known to affect ion channels.

  • Class IA antiarrhythmic agents: quinidine, procainamide, disopyramide
  • Class IC antiarrhythmic agents: propafenone
  • Class III antiarrhythmic agents: amiodarone, bretylium, dofetilide, n-acetylprocainamide, sematilide, sotalol
  • Psychotropic agents: tricyclic antidepressants, tetracyclic antidepressants, phenothiazines, haloperidol
  • Antihistamines: astemizole, terfenadine
  • Antibiotics: erythromycin, trimethoprim-sulfamethoxazole
  • Antifungals: ketoconazole, itraconazole
  • Serotonin antagonists: ketanserin, zimeldine
  • Chemotherapeutics: pentamidine, anthracyclines
  • Miscellaneous: bepridil, cisapride, prednisone, prenylamine, probucol, chloral hydrate
  • Toxins and poisons: organophosphate insecticides, anthopleurin-A, liquid protein diets, some herbs

A more complete list of drugs that can affect the QT interval is available on the University of Arizona Center for Education and Research on Therapeutics QT Drug Listhttp://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm .

Electrolyte Abnormalities

Electrolyte abnormalities can result in prolongation of the QT interval and are of special concern for those with underlying LQTS. These include the following conditions:

  • Hypokalemia
  • Hypocalcemia
  • Hypomagnesemia

Additional Factors

Several additional factors can prolong the QT interval, including:

  • Significant myocardial ischemia
  • Cerebrovascular accident, such as a subarachnoid hemorrhage
  • Increased intracranial pressure
  • Hypothermia