Review
Clinical and therapeutic aspects of congenital and acquired long QT syndrome

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Abstract

The long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram. It is associated with precipitation of a polymorphic ventricular tachycardia, torsade de pointes, which may cause sudden death. The syndrome is a disorder of cardiac repolarization caused by the alterations in the transmembrane potassium and sodium currents. Six genetic loci for the congenital forms of the syndrome have been identified; sporadic cases occur because of spontaneous mutations. Acquired causes of the long QT syndrome include drugs, electrolyte imbalance, toxins, marked bradycardia, subarachnoid hemorrhage, stroke, myocardial ischemia, protein-sparing fasting, autonomic neuropathy, and human immunodeficiency virus disease. Clinical symptoms are the result of the precipitation of torsade de pointes and range from such minor symptoms as dizziness to syncope and sudden death. Short-term treatment is aimed at preventing the recurrences of torsade de pointes and includes intravenous magnesium and potassium administration, temporary cardiac pacing, and correction of electrolyte imbalance; rarely, intravenous isoproterenol is indicated. Long-term management includes use of beta-blockers, permanent pacemaker placement, and cardioverter-defibrillator implantation. Asymptomatic patients are treated if under the age of 40 years at the time of diagnosis.

Section snippets

Cause

The QT interval can be prolonged by slowing outward repolarizing potassium currents, enhancing inward calcium currents, or slowing the inactivation of inward depolarizing sodium currents. The long QT syndrome is caused by similar types of changes in transmembrane ionic currents 5, 6, 7, 8.

Electrocardiographic manifestations

By definition, the long QT syndrome is characterized by a prolonged QTc interval on the surface electrocardiogram. Other electrocardiographic features, including increased QT dispersion and T- and U-wave abnormalities, are common 36, 37, 38, 39, 40, 41 (Figure 1). The QTc interval is not only prolonged but also more variable; thus, QT dispersion, a measure of the QT interval variability, is increased (36). T waves may be larger, prolonged, or bizarre looking, with a notched, bifid, or biphasic

Diagnosis

The diagnosis of the long QT syndrome is made by clinical characteristics, electrocardiographic findings, and family history. Unexplained syncope or sudden cardiac death in a child or young adult should suggest the diagnosis. The criteria in Table 349, 56 provide a quantitative approach to the diagnosis and classify patients as having a low, intermediate, or high probability of the syndrome. In borderline cases, exercise testing may be performed because of possible abnormal lengthening of the

Short-term treatment

Many episodes of torsade de pointes are short lived and terminate spontaneously. However, a prolonged episode may result in marked hemodynamic compromise, and immediate cardioversion should be implemented. Short-term treatment of the syndrome is aimed at preventing the recurrence of torsade de pointes, and includes administration of intravenous magnesium sulfate and temporary transvenous cardiac pacing, but rarely administration of intravenous isoproterenol. Intravenous magnesium and temporary

Long-term treatment of the congenital long QT syndrome

Long-term treatment has as its purpose shortening the QTc interval and preventing recurrences of torsade de pointes, treatment that reduces 10-year mortality to 3% to 4%. Treatment options include beta-blockers, permanent pacemaker placement, and implantation of a cardioverter-defibrillator. Recent advances in understanding the genetics of the congenital long QT syndrome have led to interest in the development of mutation-specific therapies.

Long-term treatment of the acquired long QT syndrome

Patients with torsade de pointes resulting from the acquired causes of a prolonged QT interval often require only acute treatment along with withdrawal of any offending agents and correction of any electrolyte imbalance. Long-term treatment is generally not required in these patients, because the QTc interval often becomes normal once the underlying cause is treated. Use of agents that prolong the QTc interval directly, or indirectly by causing electrolyte imbalance, should be avoided in

References (88)

  • C Machado et al.

    Torsade de pointes as a complication of subarachnoid hemorrhagea critical reappraisal

    J Electrocardiol

    (1997)
  • J.S Fisler

    Cardiac effects of starvation and semistarvation dietssafety and mechanisms of action

    Am J Clin Nutr

    (1992)
  • I.A Khan et al.

    Torsade de pointesa case with multiple variables

    Am J Emerg Med

    (1999)
  • G Malfatto et al.

    Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome

    J Am Coll Cardiol

    (1994)
  • P.J Schwartz et al.

    Electrical alternation of the T waveclinical and experimental evidence of its relationship with the sympathetic nervous system and with the long QT syndrome

    Am Heart J

    (1975)
  • L.L Herman et al.

    Long QT syndrome presenting as a seizure

    Am J Emerg Med

    (1992)
  • M.H Lehmann et al.

    Age-gender influence on the rate-corrected QT interval, and the QT-heart rate relation in families with genotypically characterized long QT syndrome

    J Am Coll Cardiol

    (1997)
  • S Viskin et al.

    Mode of onset of torsade de pointes in congenital long QT syndrome

    J Am Coll Cardiol

    (1996)
  • P.J Schwartz

    Idiopathic long QT syndromeprogress and questions

    Am Heart J

    (1985)
  • A.J Moss et al.

    Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome

    Am J Cardiol

    (1999)
  • A.A Wilde et al.

    Auditory stimuli as a trigger for arrhythmic events differentiates HERG-related (LQT2) patients from KVLQT1-related patients

    J Am Coll Cardiol

    (1999)
  • W.M Jackman et al.

    The long QT syndromea critical review, new clinical observation and a unifying hypothesis

    Prog Cardiovasc Dis

    (1988)
  • R.B Vukmir et al.

    Torsade de pointes therapy with phenytoin

    Ann Emerg Med

    (1991)
  • M Eldar et al.

    Permanent cardiac pacing in patients with the long QT syndrome

    J Am Coll Cardiol

    (1987)
  • M Eldar et al.

    Combined use of beta-adrenergic blocking agents and long-term cardiac pacing for patients with the long QT syndrome

    J Am Coll Cardiol

    (1992)
  • S Viskin et al.

    Rate smoothing with cardiac pacing for preventing torsade de pointes

    Am J Cardiol

    (2000)
  • J Kron et al.

    The automatic implantable cardioverter-defibrillator in young patients

    J Am Coll Cardiol

    (1990)
  • T Kato et al.

    Nicorandil, a potent cardioprotective agent, reduces QT dispersion during coronary angioplasty

    Am Heart J

    (2001)
  • P.J Schwartz

    The long QT syndrome

    Curr Probl Cardiol

    (1997)
  • M Reardon et al.

    QT-interval changes with age in an overtly healthy population

    Clin Cardiol

    (1996)
  • A.J Moss et al.

    The long QT syndromeProspective longitudinal study of 328 families

    Circulation

    (1991)
  • W Zareba et al.

    Influence of genotype on the clinical course of the long QT syndrome

    N Engl J Med

    (1998)
  • C Romano et al.

    Aritmie cardiache rare dellā€™eta pediatrica

    Clin Pediatr

    (1963)
  • O.C Ward

    A new familial cardiac syndrome in children

    J Irish Med Assoc

    (1964)
  • K Hashiba et al.

    The QT prolongation syndromelong-term follow-up study of 13 families with Romano-Ward syndrome

    Heart Vessels Suppl

    (1987)
  • M.T Keating et al.

    Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene

    Science

    (1991)
  • N Neyroud et al.

    A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielson cardioauditory syndrome

    Nat Genet

    (1997)
  • J.J Schott et al.

    Mapping of a gene for long QT syndrome to chromosome 4q25-27

    Am J Hum Genet

    (1995)
  • I Splawski et al.

    Mutations in the hminK gene cause long QT syndrome and suppress IKs function

    Nat Genet

    (1997)
  • J.L Geelen et al.

    Molecular genetics of inherited long QT syndromes

    Eur Heart J

    (1998)
  • I Splawski et al.

    Spectrum of mutations in long QT syndrome genesKVLQT1, HERG, SCN5A, KCNE1, and KCNE2

    Circulation

    (2000)
  • W Haverkamp et al.

    The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugsclinical and regulatory implications. Report on a policy conference of the European Society of Cardiology

    Eur Heart J

    (2000)
  • J.S Mitcheson et al.

    A structural basis for drug-induced long QT syndrome

    Proc Natl Acad Sci

    (2000)
  • G.F Tomaselli et al.

    Electrophysiological remodeling in hypertrophy and heart failure

    Cardiovasc Res

    (1999)
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