Journal ArticleDOI
Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate : implications for gene-specific therapy
Peter J. Schwartz,Silvia G. Priori,Emanuela H. Locati,Carlo Napolitano,Francesco Cantù,Jeffrey A. Towbin,Mark T. Keating,Hicham Hammoude,Arthur M. Brown,Ling Sing K. Chen,Thomas J. Colatsky +10 more
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TLDR
This is the first study to demonstrate differential responses of LQTS patients to interventions targeted to their specific genetic defect, and it is suggested that LQT3 patients may be more likely to benefit from Na+ channel blockers and from cardiac pacing because they would be at higher risk of arrhythmia at slow heart rates.Abstract:
Background The genes for the long QT syndrome (LQTS) linked to chromosomes 3 (LQT3) and 7 (LQT2) were identified as SCN5A, the cardiac Na+ channel gene, and as HERG, a K+ channel gene. These findings opened the possibility of attempting gene-specific control of ventricular repolarization. We tested the hypothesis that the QT interval would shorten more in LQT3 than in LQT2 patients in response to mexiletine and also in response to increases in heart rate. Methods and Results Fifteen LQTS patients were studied. Six LQT3 and 7 LQT2 patients were treated with mexiletine, and its effects on QT and QTc were measured. Mexiletine significantly shortened the QT interval among LQT3 patients (QTc from 535±32 to 445±31 ms, P<.005) but not among LQT2 patients (QTc from 530±79 to 503±60 ms, P=NS). LQT3 patients (n=7) shortened their QT interval in response to increases in heart rate much more than LQT2 patients (n=4) and also more than 18 healthy control subjects (9.45±3.3 versus 3.95±1.97 and 2.83±1.33, P<.05; data e...read more
Citations
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2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)
TL;DR: In this article, the authors proposed AMIOdarone versus implantable cardioverter-defibrillator (ICD-DV) for the treatment of atrial fibrillation.
Journal ArticleDOI
2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.
Silvia G. Priori,Carina Blomström-Lundqvist,Andrea Mazzanti,Nico A. Blom,Martin Borggrefe,John Camm,Perry M. Elliott,Donna Fitzsimons,Robert Hatala,Gerhard Hindricks,Paulus Kirchhof,Keld Kjeldsen,Karl Heinz Kuck,Antonio Hernández-Madrid,Nikolaos Nikolaou,Tone M. Norekvål,Christian Spaulding,Dirk J. van Veldhuisen +17 more
TL;DR: This poster presents a probabilistic procedure to determine the best method for selecting a single drug to treat atrial fibrillation-like symptoms in patients with a history of atrialfibrillation.
Journal ArticleDOI
Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.
Qing Wang,Mark E. Curran,Igor Splawski,Timothy C. Burn,J. M. Millholland,T. J. VanRaay,Jiaxiang Shen,Katherine W. Timothy,Vincent Gm,Vincent Gm,T. De Jager,Peter J. Schwartz,J.A. Towbin,Arthur J. Moss,Donald L. Atkinson,Gregory M. Landes,Timothy D. Connors,M T Keating +17 more
TL;DR: In this article, positional cloning was used to establish KVLQT1 as the chromosome 11-linked LQT 1 gene responsible for the most common inherited cardiac arrhythmia.
Journal ArticleDOI
Genotype-Phenotype Correlation in the Long-QT Syndrome Gene-Specific Triggers for Life-Threatening Arrhythmias
Peter J. Schwartz,Silvia G. Priori,Carla Spazzolini,Arthur J. Moss,G. Michael Vincent,Carlo Napolitano,Isabelle Denjoy,Pascale Guicheney,Günter Breithardt,Mark T. Keating,Jeffrey A. Towbin,Alan H. Beggs,Paul A. Brink,Arthur A.M. Wilde,Lauri Toivonen,Wojciech Zareba,Jennifer L. Robinson,Katherine W. Timothy,Valerie A. Corfield,Duangrurdee Wattanasirichaigoon,Clive Corbett,Wilhelm Haverkamp,Eric Schulze-Bahr,Michael H. Lehmann,Ketty Schwartz,Philippe Coumel,Raffaella Bloise +26 more
TL;DR: Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner, allowing new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene- specific approaches.
Journal ArticleDOI
HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.
Silvia G. Priori,Arthur A.M. Wilde,Minoru Horie,Yongkeun Cho,Elijah R. Behr,Charles I. Berul,Nico A. Blom,Josep Brugada,Chern En Chiang,Heikki V. Huikuri,Prince J. Kannankeril,Andrew D. Krahn,Antoine Leenhardt,Arthur J. Moss,Peter J. Schwartz,Wataru Shimizu,Gordon F. Tomaselli,Cynthia M. Tracy +17 more
TL;DR: Developed in partnership with the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology, and the Asia Pacific Heart Rhythm society (APHRS).
References
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Journal ArticleDOI
A mechanistic link between an inherited and an acquird cardiac arrthytmia: HERG encodes the IKr potassium channel
TL;DR: The finding that HERG encodes IKr channels provides a mechanistic link between certain forms of inherited and acquired LQT, and that an additional subunit may be required for drug sensitivity.
Journal ArticleDOI
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome
Mark E. Curran,Igor Splawski,Katherine W. Timothy,Vincent Gm,Eric D. Green,Keating Mt,Keating Mt +6 more
TL;DR: In this article, the authors investigated patients with long QT syndrome (LQT), an inherited disorder causing sudden death from a ventricular tachyarrythmia, torsade de pointes.
Journal ArticleDOI
SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome
Qing Kenneth Wang,Jiaxiang Shen,Jiaxiang Shen,Igor Splawski,Donald L. Atkinson,Donald L. Atkinson,Zhizhong Li,Jennifer L. Robinson,Arthur J. Moss,Jeffrey A. Towbin,Mark T. Keating +10 more
TL;DR: Genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene, and single strand conformation polymorphism and DNA sequence analyses suggest that mutations in SCN 5A cause chromosome 3-linked LQt and indicate a likely cellular mechanism for this disorder.
Journal ArticleDOI
Diagnostic criteria for the long QT syndrome. An update.
TL;DR: The availability of effective therapy for this often lethal disease emphasizes the importance of early and accurate diagnosis, and there is frequently a delay in the diagnosis of LQTS, and patients with syncope are often misdiagnosed.
Journal ArticleDOI
Molecular mechanism for an inherited cardiac arrhythmia
TL;DR: Persistent inward sodium current explains prolongation of cardiac action potentials, and provides a molecular mechanism for this form of congenital long-QT syndrome.
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