S-63
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A molecular approach to the
treatment of cardiac arrhythmias. The last chance for poetry
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Peter J. Schwartz*, Silvia G.
Priori°.
*Cattedra di Cardiologia Universita degli Studi di Pavia,
*Dipartimento di Cardiologia, Policlinico S. Matteo IRCCS,
°Laboratori di Cardiologia Molecolare ed Elettrofisiologia, Fondazione "S.
Maugeri" IRCCS, Pavia, Italy
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Abstract
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The rapid development of molecular biology, coupled
with a growing series of studies linking classic clinical knowledge to the new
methodological opportunities, is opening the possibility of a molecular approach to the
treatment of cardiac arrhythmias. The best paradigm for this new situation is offered by
the congenital long QT syndrome (LQTS), in which the realization that all the disease
genes identified so far encode for ion channels involved in the control of repolarization
has been rapidly followed by the understanding of the specific electrophysiologic
consequences of the various mutations. This opens a previously unforeseen array of new
therapeutic options, some of which are not yet possible today because of the need to
complete some methodological steps (e.g. the proper transfection of cardiac myocytes
harboring mutated genes with wild type genes, or the best and safest way to achieve
overexpression of either wild type genes or of their protein products). Another clinical
example is that of heart failure, where growing evidence points to underexpression of
specific repolarizing currents, namely IK1 and Ito, as one of the mechanisms underlying
abnormalities of ventricular repolarization and, hence, the propensity for
life-threatening arrhythmias responsible for the frequent and often premature sudden
cardiac death encountered by these patients.
These are exciting, and intellectually rewarding, possibilities. However, the current
reality is that the most effective ways which have proved successful in reducing
cardiovascular mortality are actually represented by rather gross and unsophisticated
interventions.
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Key Words
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Treatment of arrhythmias – mechanisms
molecular arrhythmology, congenital long QT syndrome, gene disease, heart failure, sudden
death, cellular changes in ion channels, electrical remodeling, CAST trial, Sicilian
gambit, SWORD trial, R
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