The proposed research is a multidisciplinary, multicenter, collaborative study to investigate the clinical, cardiac, and genetic aspects of the Long QT Syndrome (LQTS) - a heritable disorder with delayed repolarization, episodic malignant arrhythmias with syncope and sudden death, and recently demonstrated gene linkage in a large pedigree. The five-year research plan consists of: 1) investigation of genetic heterogeneity in LQTS by testing for Harvey-ras-1 gene linkage in the existing well-characterized LQTS families with evidence of a major gene by segregation analysis; in LQTS families that do not show Harvey-ras- 1 linkage, a search for other closely linked genetic markers will be initiated; 2) exploration by segregation analysis of the likelihood that a second gene coexists with the Harvey-ras-1 gene to explain a more malignant disease process in some LQTS families than in others; 3) establishment of normal standards for 6 quantitative repolarization parameters on a healthy population (n=4,000) using digitized ECG recordings, and biomedical and statistical techniques with adjustment for age, gender, race, and heart rate; 4) continuation of existing LQTS registry with ongoing enrollment of new families and follow-up of new and existing LQTS pedigrees (n=370 families) in order to provide a central repository for this disorder, especially as it relates to the natural history of this disorder and ongoing genetic analyses; 5) investigation of the static (12-lead ECG) and dynamic (24-hour Holter ECG) aspects of ventricular repolarization in LQTS families showing Harvey-ras gene linkage to upgrade the ECG categorization of delayed repolarization using the Harvey-ras- 1 marker as the gold standard to identify affected and unaffected individuals; and 6) continuation of the prospective longitudinal follow-up study of LQTS families to better understand the long-term clinical course of this disorder; time-dependent survivorship analyses will be performed to evaluate the effects of various clinical features, repolarization severity (QTc length), Harvey-ras-I gene linkage, and therapeutic efficacy with antiadrenergic therapy (if data permits) on outcome event rates (syncope and sudden death) in the LQTS probands. This integrated research program offers a substantial prospect of: 1) improving the presymptomatic diagnosis and treatment of LQTS; and 2) providing a fundamental under-standing of the molecular basis of repolarization-related cardiac arrhythmias.
| Kutyifa, Valentina; Daimee, Usama A; McNitt, Scott et al. (2018) Clinical aspects of the three major genetic forms of long QT syndrome (LQT1, LQT2, LQT3). Ann Noninvasive Electrocardiol 23:e12537 |
| Auerbach, David S; Biton, Yitschak; Polonsky, Bronislava et al. (2018) Risk of cardiac events in Long QT syndrome patients when taking antiseizure medications. Transl Res 191:81-92.e7 |
| Wang, Meng; Szepietowska, Barbara; Polonsky, Bronislava et al. (2018) Risk of Cardiac Events Associated With Antidepressant Therapy in Patients With Long QT Syndrome. Am J Cardiol 121:182-187 |
| Wilde, Arthur A M; Moss, Arthur J; Kaufman, Elizabeth S et al. (2016) Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study. Circulation 134:872-82 |
| Zhang, Claire; Kutyifa, Valentina; Moss, Arthur J et al. (2015) Long-QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder. J Cardiovasc Electrophysiol 26:1039-44 |
| Zhang, Claire; Kutyifa, Valentina; McNitt, Scott et al. (2015) Identification of Low-Risk Adult Congenital LQTS Patients. J Cardiovasc Electrophysiol 26:853-858 |
| Olde Nordkamp, Louise R A; Ruwald, Martin H; Goldenberg, Ilan et al. (2014) Syncope in genotype-negative long QT syndrome family members. Am J Cardiol 114:1223-8 |
| Abu-Zeitone, Abeer; Peterson, Derick R; Polonsky, Bronislava et al. (2014) Oral contraceptive use and the risk of cardiac events in patients with long QT syndrome. Heart Rhythm 11:1170-5 |
| Abu-Zeitone, Abeer; Peterson, Derick R; Polonsky, Bronislava et al. (2014) Efficacy of different beta-blockers in the treatment of long QT syndrome. J Am Coll Cardiol 64:1352-8 |
| Mullally, Jamie; Goldenberg, Ilan; Moss, Arthur J et al. (2013) Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. Heart Rhythm 10:378-82 |
Showing the most recent 10 out of 112 publications
