Updates on the Inherited Cardiac Ion Channelopathies: From Cell to Clinical
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The inherited channelopathies are a rare, heterogeneous group of diseases with widely variable clinical presentations and courses. Systematic clinical and experimental work has led to identification of disease-causing genetic mutations and their biophysical manifestation. The process by which the knowledge base is developed, from genetic mutation, to cardiac myocyte, to whole heart, and finally to clinical presentation, has dramatically expanded our understanding of these diseases. Most importantly, we can now begin to comprehend how small changes at the genetic level can dramatically influence a patient’s clinical course.
KeywordsCardiac channelopathy Sudden cardiac death Pediatrics
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The authors have no relevant disclosures.
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- 2.•Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, et al. Prevalence of the congenital long-QT syndrome. Circulation. 2009;120(18):1761–7. This is the first population-based study investigating the prevalence of congenital long QT syndrome in Caucasian infants. PubMedCrossRefGoogle Scholar
- 3.••Itoh H, Shimizu W, Hayashi K, Yamagata K, Sakaguchi T, Ohno S, et al. Long QT syndrome with compound mutations is associated with a more severe phenotype: a Japanese multicenter study. Hear Rhythm. 2010;7(10):1411–8. This multicenter study out of Japan compared genotyped patients with single versus compound mutations and found that those patients with compound mutations were more likely to have severe phenotypes.CrossRefGoogle Scholar
- 11.••Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, et al. Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009;120(18):1752–60. This article investigates the value of mutation type as well as the gene/protein region in determining the probability of pathogenicity for mutations. They determine that mutation type, location and ethnic-specific background rates are critical in predicting pathogenicity of mutations. PubMedCrossRefGoogle Scholar
- 12.Barsheshet A, Goldenberg I, O-Uchi J, Moss AJ, Jons C, Shimizu W, et al. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to beta-blocker therapy in type-1 long QT syndrome. Circulation. 2012;125(16):1988–96.PubMedCrossRefGoogle Scholar
- 16.•Liu JF, Jons C, Moss AJ, McNitt S, Peterson DR, Qi M, et al. Risk Factors for Recurrent Syncope and Subsequent Fatal or Near-Fatal Events in Children and Adolescents With Long QT Syndrome. J Am Coll Cardiol. 2011;57(8):941–50. This study, generated from the Long QT Syndrome Registry is the first to assess traditional risk markers for cardiac events in the LQTS populations as independent predictors of subsequent syncope. PubMedCrossRefGoogle Scholar
- 17.•Spazzolini C, Mullally J, Moss AJ, Schwartz PJ, McNitt S, Ouellet G, et al. Clinical implications for patients with long QT syndrome who experience a cardiac event during infancy. J Am Coll Cardiol. 2009;54(9):832–7. In this study from the International Long QT Registry demonstrated that patients who had an aborted sudden cardia carrest during the 1st year of life were at very high risk for subsequent cardiac arrests during the next decade of life, and that beta-blockers may not be as effective as in other populations. PubMedCrossRefGoogle Scholar
- 21.••Blaufox AD, Tristani-Firouzi M, Seslar S, Sanatani S, Trivedi B, Fischbach P, et al. Congenital Long QT 3 in the Pediatric Population. Am J Cardiol. 2012;109(10):1459–65. An international multicenter review of pediatric patients with Long QT Syndrome type 3. It found that these children had severe symptoms and typically had longer QTc intervals which may be shortened with mexiletine. PubMedCrossRefGoogle Scholar
- 29.••Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol. 2010;3(4):401–8. This is a systematic review of the Short QT syndrome and reviews all relevant data starting at the molecular level and working up to clinical symptoms. PubMedCrossRefGoogle Scholar
- 38.•Amin AS, Klemens CA, Verkerk AO, Meregalli PG, Asghari-Roodsari A, de Bakker JM, et al. Fever-triggered ventricular arrhythmias in Brugada syndrome and type 2 long-QT syndrome. Neth Heart J. 2010;18(3):165–9. This article investigates the risk for ventricular arrhythmias in patients with Brugada Syndrome and Long QT Syndrome, type 2, as well as possible molecular mechanisms. PubMedCrossRefGoogle Scholar
- 43.••Priori SG, Gasparini M, Napolitano C, Della Bella P, Della Bella P, Ottonelli AG, et al. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol. 2012;59(1):37–45. This is a prospective registry designed to investigate the predictive power of EP study and ventricular tachycardia inducibility in patients with Brugada Syndrome. They found that tachycardia inducibility was not able to identify high-risk patients. PubMedCrossRefGoogle Scholar
- 54.••Watanabe H, Chopra N, Laver D, Hwang HS, Davies SS, Roach DE, et al. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med. 2009;15(4):380–3. This breakthrough article demonstrated the effectiveness of flecainide, a class 1C antiarrhythmic, in the treatment of CPVT in a mouse model as well as 2 human patients. PubMedCrossRefGoogle Scholar
- 57.••Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Hear Rhythm. 2011;8(8):1308–39. This recent consensus document clearly delineates the state of genetic testing for cardiac channelopathies and cardiomyopathies. CrossRefGoogle Scholar