Newswise — Cardiologists from the Cardiac & Vascular Institute at NYU Langone Medical Center presented new research at The Heart Rhythm Society’s 32nd Annual Scientific Sessions, May 4 -7 in San Francisco, California. Researchers presented recent findings about the value of expanding genetic screening for life threatening arrhythmia, advanced risk stratification for genetic conditions like Brugada Syndrome and the promise of novel spinal cord stimulation technology to treat atrial fibrillation. Significant research findings by NYU Langone cardiologists included:
Value of Entire Open Reading Frame Screening of RyR2. Evidence from the Italian CPVT RegistryAbstract PO6-100: Embargoed, Saturday, May 7, 2011, 9:00 AM Authors: Marina Cerrone, MD, Luciana De Giuli, PhD, Raffaella Bloise, MD, Nicola Monteforte, MD, Carlo Napolitano, MD, PhD and Silvia G. Priori, MD, PhDCatecholaminergic Polymorphic Ventricular Tachycardia. (CPVT) is characterized by arrhythmia occurring during exercise or acute emotion in individuals without structural cardiac abnormalities. This condition may cause sudden cardiac death. Gene mutations in the RyR2 cardiac ryanodine receptor are associated with the condition. In prior research, 155 different RyR2 mutations have been reported in patients with clinical manifestations of the disease. Based on the localization of these mutations it has been suggested that screening of the RyR2 gene for diagnostic purposes should be limited to certain gene regions. In order to assess whether this approach is correct, researchers screened 139 probands from a CPVT cohort and 131 affected family members to define whether the limited screening is appropriate. Researchers identified that RyR2 mutations were found in 59% of probands; all were symptomatic (40/82 survived cardiac arrest), 12/82 (15%) carried mutations outside the regions conventionally screened. 6/82 (7%) probands had mutations in the 39 exons not screened by a commercial panel of 66/105 exons. Screening of family members in 6 families identified 3 silent mutation carriers among first degree relatives. This new study shows partial screening of RyR2 in CPVT patients misses a substantial proportion of mutations. In addition, partial screening prevents the identification of silent mutation carriers leaving these patients exposed to the risk of life threatening arrhythmias.Learn more: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=47bd43f5-b65f-42c2-858a-67387fdcc255&cKey=4f424215-f8ce-47bb-b15d-d76b99c23458&mKey=%7b29F06DE6-6576-4BFC-8E3B-A7C36155D815%7d+%0d%0a
Spinal Cord Stimulation Prevents Tachypacing-Induced Atrial FibrillationAbstract PO4-117: Embargoed, Friday, May 6, 2011, 9:00 AMAuthors: Scott A. Bernstein, MD, Brian Wong, MD, Douglas Holmes, MD, Laura M. Kuznekoff, BA, Ryan Rooke, MS, Marie Älvstrand, BS, Carolina Vasquez, PhD, Rupinder Bharmi, MS, Riddhi Shah, MS, Stuart P. Rosenberg, MS, Taraneh G. Farazi, PhD, Larry Chinitz, MD and Gregory E. Morley, PhD Spinal cord stimulation has been shown to modulate atrial electrophysiology and protect against ischemia and ventricular arrhythmias. Researchers hypothesized that spinal cord stimulation may reduce susceptibility to tachypacing (TP) induced atrial fibrillation (AF). In the study, spinal cord leads were implanted in the upper thoracic spine (T1-T5) of canines and connected to pulse generators. The AV node was ablated and atrial effective refractory period (AERP) was measured at baseline and with spinal cord stimulation. In separate animals the AV node was ablated and endocardial RA and RV pacing leads were connected to dual chamber pacemakers for ambulatory atrial fibrillation induction. Custom firmware provided continuous 30 second periods of atrial tachypacing followed by 6 second sense windows. Tachypacing was interrupted by detection of atrial fibrillation (atrial rate >250 bpm) and resumed upon return to sinus rhythm. Atrial fibrillation index was defined as the fraction of time the animal did not receive tachypacing relative to the total allowable tachypacing time. The effect of spinal cord stimulation delivered intermittently on atrial fibrillation index was followed for 8 weeks and compared to the control. The atrial effective refractory period was significantly longer during spinal cord stimulation compared to baseline. Atrial fibrillation index was significantly decreased in those with spinal cord stimulation compared to those without. This data demonstrate that spinal cord stimulation prolongs the atrial effective refractory period and prevents tachypacing -induced atrial fibrillation. Learn more: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=0e24d522-4ec8-43f5-8eec-7cf4f311dd9d&cKey=8f2eb4d9-4572-4f3e-9df6-a6f997689149&mKey=%7b29F06DE6-6576-4BFC-8E3B-A7C36155D815%7d+%0d%0a
Novel Scheme for Risk Stratification and Therapy Selection in Brugada Syndrome Results of The PRELUDE Study Abstract LB-03: Embargoed, Thursday, May 5, 2011, 11:00 AM Authors: Carlo Napolitano, MD, PhD, Maurizio Gasparini, MD, Paolo Della Bella, MD, Andrea Ghidini Ottonelli, MD, Biagio Sassone, MD, Umberto Giordano, MD, Carlo Pappone, MD, Giosuè Mascioli, MD, Guido Rossetti, MD, Roberto De Nardis, MD and Silvia G Priori, MD, PhDBrugada syndrome is a genetic disease associated with increased risk of sudden cardiac death. Even though its value has been questioned, the occurrence of ventricular tachycardia and ventricular fibrillation is widely used to select candidates to receive an implantable defibrillator device for prevention of cardiac death. The PRELUDE prospective registry was designed to assess the predictive accuracy of VT/VF and to identify additional predictors of arrhythmic events in Brugada syndrome. In the study, patients with a type I electrocardiogram either at baseline or after a pharmacologic challenge and without history of cardiac arrest were enrolled. Researchers found that ventricular tachyarrhythmia in 40% of patients and VT/VF inducibility was not a predictor of arrhythmic events at follow up. Analysis showed that history of syncope and spontaneous type I electrocardiogram were associated with increased risk of events. Furthermore researchers identified ventricular refractory period <200 ms (HR 3.91) and QRS fragmentation (HR 4.94) as significant and independent predictors of arrhythmic events. The results of PRELUDE show that programmed electrical stimulation, irrespective of the number of premature beats used is not predictive of cardiac events. The study confirms the prognostic value of the presence of a spontaneous Type I electrocardiogram and history of syncope. Learn more: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=90825262-7279-442e-831b-e228c6424762&cKey=15833239-0f35-4109-9bc3-480b334ba917&mKey=%7b29F06DE6-6576-4BFC-8E3B-A7C36155D815%7d+%0d%0a
Genotype Phenotype Correlation in Patients with Plakophilin-2 Mutations Abstract PO4-97: Embargoed, Friday, May 6, 2011, 9:00 AM Author: Mirella Memmi, PhD, Nicola Monteforte, MD, Patrick Gambelli, PhD, Stefano Rovaris, BS, Raffaella Bloise, MD, Carlo Napolitano, MD, PhD and Silvia G. Priori, MD, PhDArrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is an inherited desmosomal disease characterized by fibro-fatty replacement preferentially in the right ventricular myocardium. ARVC predisposes patients with the condition to ventricular arrhythmias and sudden cardiac death. Mutations in the PKP2 gene (plakophilin-2) are the most frequently identified with the condition in the molecular diagnostic labs. The purpose of this study was to assess the clinical presentation and natural history of PKP2 mutations. Among 70 probands with ARVC diagnosis, direct sequencing of the PKP2 gene identified 19 different disease-causing mutations (11 unpublished) in 20 probands (29%) and 15 family members. Twenty-one patients showed mutations that resulted in a truncated or aberrant protein as a result of insertion-deletion, nonsense, or splice site mutations (group A); while 14 patients showed missense mutations (group B). Protein sequence alignments confirmed these mutations affect highly conserved amino acids. Researchers assessed genotype phenotype correlation in ARVC patients with PKP2 mutations. The study data shows for the first time that mutations leading to truncated proteins are associated with a worse prognosis as compared with missense mutations and their detection may play an important role for risk stratification and therapy guidance.Learn more: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=0e24d522-4ec8-43f5-8eec-7cf4f311dd9d&cKey=94122fb0-43ae-489b-8e8e-88a3f14d7574&mKey=%7b29F06DE6-6576-4BFC-8E3B-A7C36155D815%7d+%0d%0a
About NYU Langone Medical CenterNYU Langone Medical Center, a world-class patient-centered integrated academic medical center, is one of the nation’s premier centers for excellence in health care, biomedical research, and medical education. Located in the heart of Manhattan, NYU Langone is comprised of three hospitals—Tisch Hospital, a 705-bed acute-care tertiary facility, Rusk Institute of Rehabilitation Medicine, the first rehabilitation hospital in the world, with 174 beds and extensive outpatient rehabilitation programs, and the 190-bed Hospital for Joint Diseases, one of only five hospitals in the world dedicated to orthopaedics and rheumatology—plus the NYU School of Medicine, one of the nation’s preeminent academic institutions. For more information, visit http://www.med.nyu.edu/.
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