The long QT syndrome and torsade de pointes.
The LQTS is a prime example of how molecular biology, ion channel, cellular, and organ physiology, coupled with clinical observations, promise to be the future paradigm for advancement of medical knowledge. Both the congenital and acquired LQTS are due to abnormalities (intrinsic and/or acquired) of the ionic currents underlying cardiac repolarization. In this review, the continually unraveling molecular biology of congenital LQTS is discussed. The various pharmacological agents associated with the acquired LQTS are listed. Although it is difficult to predict which patients are at risk for TdP, careful assessment of the risk-benefit ratio is important before prescribing drugs known to be able to cause QT prolongation. The in vivo electrophysiological mechanism of TdP in the LQTS is described using, as a paradigm, the anthopleurin-A canine model, a surrogate for LQT3. In the LQTS, prolonged repolarization is associated with increased spatial dispersion of repolarization. Prolongation of repolarization also acts as a primary step for the generation of EADs. The focal EAD induced triggered beat(s) can infringe on the underlying substrate of inhomogeneous repolarization to initiate polymorphic reentrant VT, sometimes having the characteristic twisting QRS configuration known as TdP. The review concludes by discussion of the clinical manifestations and current management of both the congenital and acquired LQTS. The initial therapy of choice for the large majority of patients with the congenital LQTS is a beta-blocking drug. This therapy seems to be effective in LQT1 and LQT2 patients, but may not be as effective in LQT3 patients. Other therapeutic options include pacemakers, cervicothoracic sympathectomy, and the implantable cardioverter defibrillator. Recent molecular genetic studies have suggested several genotype specific therapies; however, long-term efficacy data are not available.
el-Sherif
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Department of Medicine, State University of New York Health Science Center, Brooklyn 11203, USA. elsherif.nabil@brooklyn.va.gov
Turitto
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D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D004562:Electrocardiography; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008133:Long QT Syndrome / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D016171:Torsades de Pointes / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000503:physiopathology