Medtronic Study Detects Gene Associated with Sudden Cardiac Death

Medtronic plc (NYSE: MDT) todayannounced first-of-its-kind findings from two independent studies thathave identified a gene associated with life-threatening abnormal heartrhythms. The study results were presented in a hotline session at the2015 European Society of Cardiology (ESC) Congress in London. The studies evaluated genetic "markers" to determine which geneabnormalities may be associated with dangerous heart rhythms that canlead to sudden cardiac death (SCD). The initial Medtronic DISCOVERY(Diagnostic Data Influence on Disease Management and Relation of GeneticPolymorphisms to Ventricular Tachyarrhythmia in ICD Patients) trialidentified a gene associated with SCD in patients with implantablecardioverter defibrillators (ICDs), and the second study, Oregon SuddenUnexpected Death Study (Oregon SUDS), confirmed this finding in thegeneral population. The DISCOVERY trial used ICDs to monitor patients for abnormal heartrhythms and then identified the gene associated with a 50 percentrelative risk increase in these life-threatening heart rhythms. Theseresults were confirmed by the Oregon-Sudden Unexpected Death Study(Oregon-SUDS), a community-based study that analyzed causes of SCD. "This research is vital to helping us better understand why somepatients are at higher risk of sudden cardiac death, one of the leadingcauses of death globally," said Sumeet Chugh, M.D., associate directorof the Cedars Sinai Heart Institute and lead investigator for OregonSUDS. "These findings put us one step closer to understanding thecomplexities of sudden cardiac death and may, someday, help us identifywhich patients are at risk." Patients with these life-threatening abnormal heart rhythms experienceabrupt loss of heart function that leads to death if they are nottreated immediately. An ICD is a small implantable device that is placedunder the skin to continuously monitor the heart; if it detects a severeabnormal heart rhythm, known as ventricular arrhythmia, it deliverstherapy to restore a normal heartbeat. "This is the first time a gene has been identified using ICD monitoringand then confirmed to be associated with sudden cardiac death in thegeneral population," said Professor Heiner Wieneke, principalinvestigator of the DISCOVERY trial and chief physician in theDepartment of Cardiology, Contilia Heart and Vessel Centre, St.Marien-Hospital Mülheim, Germany. "These findings are a first stepto learning more about how to determine better ways to prevent and treatthis condition." The two-part presentation started with the DISCOVERY trial, aprospective, multicenter study of 1,145 patients that investigated theassociation of single nucleotide polymorphisms (SNPs, a geneticvariation) with the occurrence of ventricular arrhythmias in patientsreceiving ICDs for primary prevention of sudden cardiac death. Datashowed that the gene GNAS holds two SNPs (c.2273C>T and c.393C>T) thatwere associated with an increased risk for ventricular tachyarrhythmias(VT) as identified by the ICDs. In the second part of the analysis, the database of blood samplescollected from 1,335 patients in the Oregon-SUDS trial was reviewed forthe presence of SNPs identified in the DISCOVERY trial. During thevalidation phase, c.393C>T was found to be associated with an increasedrisk for SCD in a general population under both additive (odds ratio[OR] =1.2 [1.0-1.4], p=0.039) and recessive (OR=1.5 [1.1-2.1], p=0.01)genetic models. The study confirmed that this SNP was associated with a50 percent increased risk of SCD. "The results presented today are part of Medtronic's efforts to betteridentify people at risk of SCD and to get them the right life-savingtherapy," said Marshall Stanton, M.D., vice president and generalmanager of Tachycardia in the Cardiac Rhythm and Heart Failure Businessat Medtronic. "Medtronic looks forward to partnering with the largerclinical research community to further our shared understanding of therisk for sudden cardiac death and how to prevent it." About the DISCOVERY Trial: The DISCOVERY Trial investigated if 7 singlenucleotide polymorphisms (SNPs) in 3 genes coding G-protein subunitswere predictive of ventricular tachyarrhythmias (VT) and SCD. The studywas conducted in 91 European centers between April 2007 and June 2011,and is sponsored by Medtronic. About the Oregon Sudden Unexpected Death (SUDS) Study: Oregon SUDS is acommunity-based SCD study in Portland being conducted by the ArrhythmiaResearch Laboratory at the Cedars-Sinai Heart Institute, Los Angeles.For more than 12 years, the study has collected detailed information onsudden cardiac arrest (SCA) cases, including blood samples toinvestigate genetic and biochemical markers of risk. The study receivessupport from the National Heart, Lung and Blood Institute (NHLBI) andthe American Heart Association.