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Novel Insights in the Congenital Long QT Syndrome

Xander H.T. Wehrens, MD; Marc A. Vos, PhD; Pieter A. Doevendans, MD; and Hein J.J. Wellens, MD
[+] Article, Author, and Disclosure Information

Acknowledgments: The authors thank Drs. R.S. Kass and A.A. Wilde for sharing their expertise.

Requests for Single Reprints: Marc A. Vos, MD, Department of Cardiology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands; e-mail, m.vos@cardio.azm.nl.

Current Author Addresses: Dr. Wehrens: Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, 630 W 168th Street, P&S 9-401, New York, NY 10032.

Drs. Vos and Doevendans: Department of Cardiology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands.

Dr. Wellens: 21 Henric van Veldekeplein, 6211 TG Maastricht, the Netherlands.

Ann Intern Med. 2002;137(12):981-992. doi:10.7326/0003-4819-137-12-200212170-00012
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Background: The congenital long QT syndrome is a potentially fatal, inherited cardiac syndrome. Early diagnosis and preventive treatment are instrumental to prevent sudden cardiac death in patients with the congenital long QT syndrome.

Purpose: To review new insights in genetics and cellular electrophysiology, as well as the current understanding of the clinical diagnosis and treatment of the congenital long QT syndrome.

Data Sources: Authors' personal databases and search of PubMed database from 1966 to 2001.

Study Selection: Experimental and clinical studies on the congenital long QT syndrome.

Data Extraction: Data from peer-reviewed studies were manually extracted, classified, and summarized.

Data Synthesis: The congenital long QT syndrome is characterized by abnormally prolonged ventricular repolarization, which predisposes patients to syncope, ventricular arrhythmias, and sudden cardiac death. The recent discovery of mutations in genes encoding ion channels has improved our understanding of the cellular origin of this condition. The congenital long QT syndrome may result from inherited defects in cardiac K+ and Na+ channels, which both result in prolongation of the ventricular action potential. The diagnosis is based on electrocardiographic and clinical criteria. Genetic screening of symptomatic patients or asymptomatic family members may identify patients at risk for life-threatening ventricular arrhythmias. β-Blocking agents are the mainstay of treatment. Certain patients may also benefit from a pacemaker or implantable cardioverter defibrillator. Recent studies suggest that genotype-specific treatment of the congenital long QT syndrome will be feasible in the near future.

Conclusions: The congenital long QT syndrome is a potentially life-threatening condition caused by mutations in genes encoding cardiac ion channels. Better understanding of the mechanisms responsible for this condition will guide genotype-specific therapy in the near future.


Grahic Jump Location
Figure 1.
Ventricular action potential and electrophysiologic effects of the congenital long QT syndrome ion channel mutations. A.++TOCa,LKrKsKsK1B. Top.LQT3SCN5Adotted lineB. Middle.KCNQ1+KsLQT1dotted lineKsB. Bottom.KCNH2+KrLQT2Krdotted line

The ventricular action potential is initiated by current flow through cardiac Na channels (depolarization, phase 0). Early repolarization (phase 1) is caused by the K current I . The action potential plateau phase (phase 2) is maintained by I , I , and I currents, and late repolarization (phase 3) is caused by current flow through I and I channels. The dotted line represents action potential prolongation, as can be observed in the congenital long QT syndrome. In case of , most mutations in the gene cause a small noninactivating sodium current that remains active during the action potential plateau phase ( ) and provides an additional depolarizing current, which prolongs repolarization. The gene encodes the slowly activating delayed rectifier K channel, which conducts the I current. In case of ( ), reduced I activity leads to action potential prolongation. The gene encodes the rapidly activating delayed rectifier K channel, which conducts the I current. In , a reduction of I causes prolongation of the repolarization phase ( ).

Grahic Jump Location
Grahic Jump Location
Figure 2.
Genotype-specific electrocardiographic (ECG) pattern in the congenital long QT syndrome. Top.LQT1ABMiddle.LQT2ABBottom.LQT3A(142)

The two most common ECG patterns: broad-based T-wave pattern ( ) and normal-appearing T-wave pattern ( ). The two most frequently encountered ECG manifestations: obvious bifid T waves ( ) and subtle bifid T wave with a second component on top of the T wave in limb and left precordial leads ( ) (or, alternatively, the second component on the downslope of T wave; not shown). Most typical ECG pattern: late-onset peaked/biphasic T-wave ( ). Modified from Zhang et al. Circulation. 2000; 102:2849-55 , with permission.

Grahic Jump Location




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Summary for Patients

When the Heart's Electrical System Goes Haywire: The Congenital Long QT Syndrome

The summary below is from the full report titled “Novel Insights in the Congenital Long QT Syndrome.” It is in the 17 December 2002 issue of Annals of Internal Medicine (volume 138, pages 981-992). The authors are XHT Wehrens, MA Vos, PA Doevendans, and HJJ Wellens.


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