370 Surgical resection of postinfarction ventricular tachycardia: a risky enterprise?

Baaten, P.J.J.; Hemel, Norbert van; Kelder, Johannes C.; Dessel, PF Van; Bakker, Jacques M.T. de; Boersma, Lucas V.A.; Wever, Eric F.D.; Swieten, Henry A. van; Defauw, Jo J.A.M.

doi:10.1016/eupace/7.supplement_1.77-b

Cited by 3 publications

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“…Several characteristics of the clinical phenotype and therapeutic responses in this report are in alignment with those previously described for LQT3 cases in infants, including both pronounced QT prolongation 32–34 and mixed efficacy in the controlling QT prolongation and resulting arrhythmias with Na + channel blockers 32–35 . For example, whereas mexiletine was effective at controlling both 2:1 atrioventricular (AV) block in a newborn with an SCN5A (P1332L) mutation 33 , neither mexiletine nor flecainide was useful in long term control of QT prolongation in a neonate with another SCN5A mutation (R1623Q) 32 . In consideration of the variable efficacy of Na + channel blockers in patients with LQT3 mutations, the development of long-QT allele-specific therapeutic strategies based on a systematic characterization of mutant channels seems to be important.…”

Section: Discussionsupporting

confidence: 83%

Characterization of a novel LQT3 variant with a selective efficacy of mexiletine treatment

Kim

Park

et al. 2019

Sci Rep

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Pathogenic variants in the human SCN5A gene encoding the a-subunit of the principle Na+ channel (Nav1.5) are associated with long QT syndrome (LQTS) 3. LQT3 patients display variable responses to Na+ channel blockers demanding for the development of variant-specific therapeutic strategies. Here we performed a combined electrophysiological analysis with in silico simulation of variant channel to elucidate mechanisms of therapeutic responsiveness. We identified a novel SCN5A variant (A1656D) in a LQTS patient with a distinct response to mexiletine resulting in suppression of non-sustained ventricular tachycardia and manifestation of premature atrial contraction. Patch clamp analysis revealed that A1656D variant exerted gain-of-function effects including hyperpolarizing shift of the voltage-dependence of activation, depolarizing shift in the voltage-dependence of inactivation, and slowing of fast inactivation. Among ranolazine, flecainide, and mexiletine, only mexiletine restored inactivation kinetics of A1656D currents. In silico simulation to assess the effect of A1656D variant on ventricular cardiac cell excitation predicted a prolonged action potential which is consistent with the prolonged QT and non-sustained ventricular tachycardia of the patient. It also predicted that only mexiletine suppressed the prolonged action potential of human ventricular myocytes expressing A1656D. These data elucidate the underlying mechanism of the distinct response to mexiletine in this patient.

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Section: Discussionsupporting

confidence: 83%

Characterization of a novel LQT3 variant with a selective efficacy of mexiletine treatment

Kim

Park

et al. 2019

Sci Rep

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Therapeutic Strategies for Long-QT Syndrome

Ruan

Liu

Napolitano

et al. 2008

Circ: Arrhythmia and Electrophysiology

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Clinical Characteristics and Genetic Background of Congenital Long-QT Syndrome Diagnosed in Fetal, Neonatal, and Infantile Life

Horigome

Nagashima

Sumitomo

et al. 2010

Circ: Arrhythmia and Electrophysiology

109

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Background-Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. Methods and Results-Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (nϭ18), the neonatal period (nϭ31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (nϭ9). Clinical presentation of LQTS included sinus bradycardia (nϭ37), ventricular tachycardia/torsades de pointes (nϭ27), atrioventricular block (nϭ23), family history of LQTS (nϭ21), sudden cardiac death/aborted cardiac arrest (nϭ14), convulsion (nϭ5), syncope (nϭ5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (nϭ11), LQT2 (nϭ11), LQT3 (nϭ6), and LQT8 (nϭ1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (nϭ14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of ␤-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. Conclusions-Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded. (Circ Arrhythm Electrophysiol. 2010;3:10-17.)

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370 Surgical resection of postinfarction ventricular tachycardia: a risky enterprise?

Cited by 3 publications

References 0 publications

Characterization of a novel LQT3 variant with a selective efficacy of mexiletine treatment

Characterization of a novel LQT3 variant with a selective efficacy of mexiletine treatment

Therapeutic Strategies for Long-QT Syndrome

Clinical Characteristics and Genetic Background of Congenital Long-QT Syndrome Diagnosed in Fetal, Neonatal, and Infantile Life

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