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Program&Abstracts

ResearchInstitute–MUHC1001Decarieblvd.Montreal(Qc)H4A3J1

April27th,2017

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Organizing Committee Dr. Jacques Genest, Chair

Dr. Jonathan Afilalo Dr. Negareh Mousavi

Dr. Dominique J. Favreau Ms. Giorgina Ciavarella

Scientific Committee Dr. Jacques Genest Dr. Jonathan Afilalo

Dr. Negareh Mousavi Dr. Dominique J. Favreau

Judging Panel Dr. Jonathan Afilalo

Dr. Lorraine Chalifour Dr. Stella Daskalopoulou

Dr. James Engert Dr. Jacques Genest Dr. Nadia Giannetti

Dr. Robert Scott Kiss Dr. Christopher Labos Dr. Stephanie Lehoux Dr. Negareh Mousavi

Dr. Pierre Paradis Dr. Igal Sebag

Dr. Allan Sniderman Dr. George Thanassoulis

Dr. Annabel Chen-Tournoux

Our sincere thanks to our judges for their expertise in scoring the

abstracts submitted!

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Table of content Table of content .................................................................................................. 3 Cme accredited event ......................................................................................... 4 Acknowledgement of institutional sponsors ................................................... 5 Schedule .............................................................................................................. 6 Oral presentations abstracts ........................................................................... 10 Poster presentations abstracts ....................................................................... 24 Acknowledgements .......................................................................................... 79

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CME Accredited Event This event is approved for up to 5.0 credits by the Office for Continuing Health Professional Education (CHPE). The Office for CHPE, Faculty of Medicine, McGill University is fully accredited by the Committee on Accreditation of Canadian Medical Education (CACME).

This event is an Accredited Group Learning Activity as defined by the Maintenance of Certification program of the Royal College of Physicians and Surgeons of Canada.

Through an agreement between the Royal College of Physicians and Surgeons of Canada and the American Medical Association, physicians may convert Royal College MOC credits to AMA PRA Category 1 Credits™. Information on the process to convert Royal College MOC credit to AMA credit can be found at www.ama-assn.org/go/internationalcme.

Each physician should claim only credit commensurate with the extent of his or her participation in the activity.

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Acknowledgement of Institutional Sponsors We acknowledge and greatly appreciate the support and involvement of our institutional sponsors as an integral part of the McGill Cardiovascular Research Day.

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Schedule Thursday, April 27th, 2017

8:00 – 8:15 Registration ES1 Atrium

8:15 – 8:30 Opening Remarks Dr. Ernesto Schiffrin ES1 Auditorium

8:30 – 9:30 Oral Presentations Session A Chairs Chairs : Dr. Nadia Giannetti & Dr. Igal Sebag

ES1 Auditorium

9:30 – 10:00 Break ES1 Atrium

10:00 – 11:00 Oral Presentations Session B Chairs : Dr. Negareh Mousavi & Dr. Jonathan Afilalo

ES1 Auditorium

11:00 – 12:00 Poster Presentations ES1 Atrium

12:00 – 1:00

2016 Artur & Louis Lucian Award Lecture From bedside to bench and back, my career in academic medicine BRIAN KOBILKA, MD 2012 Nobel Prize in Chemistry laureate Professor of Molecular and Cellular Physiology, and Hélène Irwin Fagan Chair in Cardiology at Stanford University School of Medicine

ES1 Auditorium

1:00 – 2:00 Lunch ES1 Atrium 2:00 – 3:00 Poster Presentations ES1 Atrium

3:00 – 3:15 Highlights of the research programs Dr. Ariane Marelli – Research Institute – MUHC Dr. Jonathan Afilalo – Jewish General Hospital

ES1 Auditorium

3:15 – 4:30 Oral Presentations Session C Chair : Dr. Ariane Marelli

ES1 Auditorium

4:30 – 5:30 Cocktails ES1 Atrium

5:30 – 6:00 Awards / Closing remarks ES1 Atrium

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Oral Presentations (Abstracts on pages 10-23) 8:30 – 8:45 Basic Science #14: Antoine Caillon: Gamma delta t cells

mediate angiotensin ii-induced hypertension and vascular injury

8:45 – 9:00 Clinical or Population Health #25: Melissa Bendayan: Patient-Level Predictors of Bleeding in Older Adults Undergoing Transcatheter or Surgical Aortic Valve Replacement

9:00 – 9:15 Clinical or Population Health #35: Mehdi Afshar: Risks of Incident Cardiovascular disease with High Lipoprotein(a) with and without High LDL-C - The Framingham Heart Study

9:15 – 9:30 Basic Science #22: Anouar Hafiane: ATP Binding Cassette A1 (ABCA1) Mediates Microparticle Formation during High-Density Lipoprotein (HDL) Biogenesis

9:30 – 10:00 Coffee Break

10:00 – 10:15 Basic Science #15: Ku-Geng Huo: In vivo miR-431 inhibition protects against vascular damage and hypertension

10:15 – 10:30 Clinical or Population Health #26: Fei Wang: Heart failure Hospitalization in Adults with Congenital Heart Diseases: what predicts it and how does it affect mortality?

10:30 – 10:45 Clinical or Population Health #40: Sarah Cohen: Exposure to Low-Dose Ionizing Radiation from Cardiac Procedures and Risk of Malignancy in Adults with Congenital Heart Disease

10:45 – 11:00 Clinical or Population Health #61: Hao Yu Chen: Genome-wide Association Study and Replication in up to 157,107 Individuals Identifies a Novel Genetic Locus for Aortic Stenosis

Poster Presentations (Abstracts on pages 24-78) 11:00 – 12:00 Poster presentations

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2016 Artur & Louis Lucian Award Lecture

Brian Kobilka, MD

2012 Nobel Prize in Chemistry laureate

Professor of Molecular and Cellular

Physiology Hélène Irwin Fagan Chair in Cardiology

Stanford University School of Medicine

Brian Kobilka, MD is Professor of Molecular and Cellular Physiology, and Hélène Irwin Fagan Chair in Cardiology at Stanford University School of Medicine. He received a Bachelor of Science Degrees in Biology and Chemistry from the University of Minnesota, Duluth in 1977. He graduated from Yale University School of Medicine in 1981, and completed residency training in Internal Medicine at the Barnes Hospital, Washington University School of Medicine, St. Louis, Missouri in 1984. From 1984-1989 he was a postdoctoral fellow in the laboratory of Robert Lefkowitz at Duke University. In 1990 he joined the faculty of Medicine and Molecular and Cellular Physiology at Stanford University. Research in the Kobilka lab focuses on the structure and mechanism of action of G protein coupled receptors (GPCRs), which constitute the largest family of receptors for hormones and neurotransmitters in the human genome. GPCRs are the largest group of targets for new therapeutics for a very broad spectrum of diseases. In 2012, Kobilka was awarded the Nobel Prize in Chemistry for his work on GPCRs. He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences.

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Poster Presentations (Abstracts on pages 24-78) 2:00 – 3:00 Poster presentations

Highlights of the research programs 3:00 – 3:15 Dr. Ariane Marelli – Research Institute – MUHC

Dr. Jonathan Afilalo – Jewish General Hospital

Oral Presentations (Abstracts on pages 10-23) 3:15 – 3:30 Basic Science #16: Tom Reid: The Shunt Pathway:

Biochemical and molecular evidence of a novel mechanism for cholesterol homeostasis in hepatocytes

3:30 – 3:45 Clinical or Population Health #29: Ahmed Al Turki: Predicting Electrocardiographic and Echocardiographic Response to Cardiac Resynchronization Therapy: the Use of Strict Left Bundle Branch Block Criteria

3:45 – 4:00 Clinical or Population Health #34: Kim Phan: Arterial stiffness is a better early predictor for pre-eclampsia than angiogenic biomarkers and uterine artery Doppler ultrasound

4:00 – 4:15 Basic science #43: George Makhoul: Human Amniotic Stromal Cells Encapsulated in a Chitosan/Hyaluronic Acid Based Platform Proliferate and Increase Cardiac Function in a Rat Myocardial Infarction Model

4:15 – 4:30 Clinical or Population Health #59: Lior Bibas: Sarcopenia and Mortality after Cardiac Transplantation

Cocktails 4:30 – 5:30 Cocktails

Awards & Closing Remarks 5:30 – 6:00 Awards & Closing Remarks

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Oral presentations

abstracts

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#14-BasicScienceGammadeltatcellsmediateangiotensinii-inducedhypertensionandvascularinjury

Antoine Caillon PhD1 Muhammad Oneeb Rehman Mian PhD1; Julio C. Fraulob-Aquino PhD1; Ku-Geng Huo1; TliliBarhoumiPhD1;SofianeOuerdMSc1,PeterR.SinnaeveMD,PhD,FSEC3;PierreParadisPhD1andErnestoL.SchiffrinMD,PhD,FRSC,FRCPC,FACP,FAHA1,2 1LadyDavis Institute forMedicalResearch,and2DepartmentofMedicine, SirMortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Québec, Canada; 3UZ Leuven Gasthuisberg,UniversityofLeuven,Leuven,Belgium.

Background:Innateantigen-presentingcellsandadaptiveimmuneTcellshavebeenimplicatedinthe development of hypertension. However, the T-lymphocyte subsets involved in thepathophysiologyofhypertension remainunclear.There is a small subsetof “innate-like”T cellsexpressing the γδ T cell receptor (TCR) rather than the αβ TCR that could play a role in theinitiationof the immune response inhypertension. It is unknownwhether gammadeltaT cellscontribute to the development of hypertension. We aimed to determine whether angiotensin(Ang) IIcausedkineticchanges ingammadeltaTcells,whetherdeficiency inγδTcellsbluntedAng II-induced hypertension, vascular injury and T-cell activation, and whether γδ T cells areassociatedwithhumanhypertension.Methods:MaleC57BL/6wild-type(WT)andTcrδ-/-mice,whicharedevoidofγδTcells,orWTmice injected IPwith control isotype IgGor γδT cell-depleting antibodies,were infusedor notwith Ang II (490 ng/kg/min, SC) for 3, 7 or 14 days. T cell profiling was determined by flowcytometry,systolicbloodpressure(SBP)bytelemetryandmesenteryarteryendothelialfunctionby pressurizedmyography. TCR δ constant region gene expression levels and clinical data of awholebloodgeneexpressionmicroarraystudyincludingnormotensiveandhypertensivesubjectswereusedtodemonstrateanassociationbetweenγδTcellsandSBP.Results: Seven- and 14-day Ang II infusion increased γδ T cell numbers and activation in thespleen of WT mice (P

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#15-BasicScienceInvivomiR-431inhibitionprotectsagainstvasculardamageandhypertension

Ku-GengHuo1, JulioC.Fraulob-Aquino1,TliliBarhoumi1,ChantalRicher3,SuellenC.Coelho1,SofianeOuerd1,AntoineCaillon1, Mathieu Lajoie3, Daniel Sinnett3,4, Pierre Paradis1, Ernesto L. Schiffrin1,2 1Vascular and HypertensionResearchUnit,LadyDavisInstituteforMedicalResearch,2DepartmentofMedicine,SirMortimerB.Davis-JewishGeneralHospital, McGill University, 3Division of Hematology-Oncology, Research Center, CHU Ste-Justine, 4Department ofPediatrics,FacultyofMedicine,UniversitédeMontréal,Montréal,Canada

Background: Vascular injury is an early manifestation and a cause of end-organ damage inhypertension.microRNAs (miRNAs) play an important role in cardiovascular disease, but theirimplicationinvascularinjuryremainsunclear.Inthisstudy,weusedRNAsequencingandsystemsbiology to identifymiRNAs and its targets thatmediate global gene expression changes in thecourseofvascularinjuryinangiotensin(Ang)II-inducedhypertension.Methods and results: Ten-week-oldmaleC57BL/6micewere infusedornotwithAng II for 14days.Bloodpressure(BP)wasmeasuredbytelemetryandsmallmesentericartery(MA)functionand mechanic by myography. Total RNA was extracted from the MA for small and total RNAsequencing.Differentiallyexpressed(DE)miRNAs(23upand12down)andmRNAs(550upand256down)wereidentified.InteractionsbetweenDE-miRNAsandinverselyexpressedDE-mRNAsand between DE-transcription factors (TF) and DE-genes were analyzed and presented inmolecularnetworks.SeventeenupregulatedmiRNAsarelocatedinaconservedmiRNAclusteroftheDlk1-Dio3region,9ofwhichhadexpressionlevelscorrelatedwithBP(P

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#16-BasicScienceThe Shunt Pathway: Biochemical and molecular evidence of a novelmechanismforcholesterolhomeostasisinhepatocytes

TomReid -Research Instituteof theMcGillUniversityHealthCentre Dr.RobertScottKiss -Research Instituteof theMcGillUniversityHealthCentreDr.AllanSniderman-ResearchInstituteoftheMcGillUniversityHealthCentre

The traditional model for intracellular cholesterol homeostasis dictates that low densitylipoprotein (LDL) particles are taken up into cells via the LDL receptor (LDLR), wherein thecholesterol from the particle interacts with a rapidly equilibrating regulatory pool in theendoplasmicreticulum.ThisresultsindecreasedexpressionoftheLDLRand3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), the rate-limiting step of endogenous cholesterolsynthesis, resulting indecreaseddenovosynthesisof cholesteroldue to inhibitionof thesterolresponse element-binding protein 2 (SREBP-2). While this model was elucidated in fibroblastcells,theliveristheorganmostresponsibleforbothLDLclearanceandcholesterolhomeostasis,thusimplicatingthehepatocyteasamorerelevantmodelforthestudyofcholesterolmetabolism.Usingradiolabelingassaysandimmunofluorescence,thisstudycorroboratesthe“shuntpathway”model for cholesterol homeostasis that describes an LDL pathway in which LDL-derivedcholesterol does not appreciably interact with the regulatory pool at the ER, but is ratherpreferentially esterified by acyl-CoA:cholesterol acyltransferase 2 (ACAT2) and re-secreted inVLDL particles. Using 3 different hepatocyte models (IHH, HepG2 and mouse primaryhepatocytes), we observe preferential esterification of LDL derived cholesterol as well asincreased ACAT activity upon LDL loading, as measured by addition and incorporation ofradiolabeledsubstratesandintocholesteryl-ester(CE).Additionally,increaseddenovosynthesisof cholesterol upon LDL loading was also observed. Furthermore, immunofluorescence assaysconfirmedboththepreferentialcolocalizationofLDLparticleswithACAT2,aswellasthenuclearaccumulationofSREBP-2uponLDLloading.Theimplicationsofthisstudyfollowthoseofthefirstshunt pathway study, in that the conventional model for cholesterol homeostasis cannotsufficiently be applied to the liver. Moreover, therapeutic targeting of proteins involved in theshunt pathway may prove crucial for treatment of cardiovascular disease caused byatherosclerosis.KeywordsShunt,Liver,Hepatocyte,ldl,Chylomicron,Cholesterol,ACAT2

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#22-BasicScienceATP Binding Cassette A1 (ABCA1)MediatesMicroparticle Formation duringHigh-DensityLipoprotein(HDL)Biogenesis

Anouar Hafiane and Jacques Genest Cardiovascular Laboratory, Cardiology Division, McGill University HealthCentre/RoyalVictoriaHospital,Montréal,QuébecH3A1A1,Canada

Backgroundandaims:Micro-particles(MP)aresecretedbyvariouscells.Theirbiologicalrolesinhealth and in disease remain unknown. Here we describe formation of MP in the process ofABCA1-dependentcholesteroleffluxindifferentcelltypes.In Vitro Methods and results: The ATP-binding cassette transporter, subfamily A, member 1(ABCA1)istherate-limitingstepinthebiogenesisofhigh-densitylipoproteins(HDL).UsingFPLCand nanoparticle tracking analysis from media cell-based systems with overexpression andselective inactivation of ABCA1, pharmacological blockade and modulation of membranecholesterolcontent,wecharacterizedMPreleasefromvariouscelllines.WestudiedMPreleaseinBHKcells stablyexpressingABCA1undermifepristonecontrol,humanTHP-1macrophagesandHepG2cellswithout,orwithincubationwithhumanapoA-I.WehavefoundthatABCA1withoutapoA-I or with apoA-I contribute to the formation of MP. Importantly, BHK-mock cells notexpressingABCA1shownoMPrelease.AnalysisofMPreleasedfromhumanTHP-1cellsisolatedby FPLC followed by ultracentrifugation and equilibrium sucrose gradient density (2-0.5M)indicate that ABCA1 mediates the production of MPs containing cholesterol with highlyheterogeneous size distribution (50-250nm) corresponding to sucrose density range(1.10

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#25-ClinicalorPopulationHealthPatient-Level Predictors of Bleeding in Older Adults UndergoingTranscatheterorSurgicalAorticValveReplacementMelissa Bendayan - Department of ExperimentalMedicine,McGill University, Centre for Clinical Epidemiology, LadyDavis Institute, Jewish GeneralHospital SandraLauck-St.Paul'sHospital DaeHyunKim-BethIsraelDeaconessMedicalCenter ThierryLefèvre-HôpitalJacquesCartier NicoloPiazza-McGillUniversityHealthCentreKevinLachapelle-McGillUniversityHealthCentreGiuseppeMartucci-McGillUniversityHealthCentreAndreLamy-HamiltonGeneralHospitalMarinoLabinaz-OttawaHeartInstituteMarkPeterson-St.Michael'sHospitalRakeshArora-St.BonifaceHospitalNicolasNoiseux-Centrehospitalierdel'UniversitédeMontréalAndrewRassi-MassachusettsGeneralHospitalPhilippeGénéreux-HôpitalduSacré-Coeur Brian Lindman -Washington University School of Medicine Anita Asgar - Institut de Cardiologie deMontréal Caroline Kim - Beth IsraelDeaconessMedicalCenterAmandaTrnkus-CentreforClinicalEpidemiology,LadyDavisInstitute,JewishGeneralHospitalJoseMorais-Departmentof Cardiology, Jewish General Hospital Yves Langlois - Department of Cardiology, Jewish General Hospital Lawrence Rudski - Department ofCardiology,JewishGeneralHospitalJeffreyPopma-BethIsraelDeaconessMedicalCenterJohnWebb-St.Paul'sHospitalLouisPerrault-InstitutdeCardiologiedeMontréalJonathanAfilalo-DepartmentofCardiology,JewishGeneralHospital

Background: Bleeding complications are harbingers of mortality and major morbidity in patientsundergoingsurgical(SAVR)ortranscatheter(TAVR)aorticvalvereplacement.Predictionofbleedingrisk is crucial to tailor the procedural approach and implement preventative strategies. Despite thehighprevalenceoffrailtyinthispopulation,littleisknownabouttheeffectoffrailtyonbleedingrisk.Thus, we sought to define patient-level predictors of major bleeding complications in older adultsundergoingTAVRorSAVR.

Methods: We performed a post hoc analysis of the Frailty-AVR cohort study that prospectivelyenrolledolderadultsaged70yearsorolderundergoingTAVRorSAVRat14 institutions inCanada,theUnited States, andFrance.Before theprocedure,we administered a short physical performancebatteryandfrailtyquestionnaire,andascertainedcomorbidconditionsandlaboratorydata fromtheelectronic health record. For the purposes of this analysis, the primary endpointwasmajor or life-threateningbleedingduringtheindexhospitalizationdefinedaccordingtotheVARC-2criteria.

Results:Thecohortconsistedof929patientswithameanageof81.4years,ofwhich116patientshadamajorbleed(55/576[9.5%]intheTAVRgroup,61/353[17.3%]intheSAVRgroup).Patientswithmajorbleedsweremorelikelytohavegastrointestinaldiseases,arecentmyocardialinfarction,lowerbaseline platelet counts, lower baseline serum albumin, and a higher number of diseased coronaryvessels requiring bypass grafts (for those undergoing concomitant revascularization with SAVR).Frailty,definedbyeitherFried’sscaleorRockwood’sclinicalfrailtyscale,wasnotpredictiveofbleeds.Inamultivariablelogisticregressionmodel,thenumberofdiseasedcoronaryvessels(OR1.31,95%CI1.02to1.69),GIdisease(OR1.83,95%CI1.03to3.27)andserumalbumin(OR0.50,95%CI0.30to0.84)wereindependentpredictorsofmajorbleeds.Comparedtopatientswithoutamajorbleed,thosewithamajorbleedrequiredmoreredcelltransfusions(6.5vs.0.9units,P

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#26-ClinicalorPopulationHealthHeart failureHospitalization inAdultswithCongenitalHeartDiseases:whatpredictsitandhowdoesitaffectmortality?

FeiWang,MSc;AihuaLiu,PhD;SarahCohen,MD;LimingGuo,MSc;JudithTherrien,MD;ArianeMarelli,MD,MPH;McGillAdultUnitforCongenitalHeartDiseaseExcellence(MAUDEUnit)

Background: Adults with congenital heart disease (ACHD) are not cured and residual diseasepredisposethemtocongestiveheart failure(CHF).Thisstudyaimedtocalculate thecumulativeprobabilityofCHF, identifypredictorsofone-year riskofCHFandassess the impactofCHFonmortality.Method:ThecumulativeriskcohortwasderivedfromtheQuebecCHDdatabaseandconsistedof27975patientsaged18-65between1995and2010.WecalculatedthecumulativeprobabilityofCHFhospitalizationusingthePracticalIncidenceEstimatormacrotoadjustforthecompetingriskofdeath.ToassesstheimpactofCHFhospitalizationonmortality,wefirstusedpropensityscorematching to select random controls for each CHF hospitalized patient. We then compared themortality rates between the CHF patients and their matched controls.We applied nested casecontrolstudyandconductedbinarylogisticregressionanalysestoidentifythepredictorsofone-year risk of CHFhospitalization.We further used the regressionmodel to construct a clinicallyusefulriskscoringsystem(RAAID-CHF)forCHFhospitalizationtoidentifypatientsintheneedofacceleratedreferraltospecializedACHDcentres.Results: The lifetime cumulative risk of CHF hospitalization by age 65 was 33.2%. CHFhospitalizationwasassociatedwitha5foldincreaseinmortalityrisk(HazardRatio=5.4,95%CI:3.5, 8.3). Age, sex, CHD severity, CHF hospitalization history and comorbidities includingarrhythmia,pulmonaryhypertension,andcoronaryheartdiseaseintheprevious12monthsweresignificant predictors of one-year CHF hospitalization. The RAAID-CHF had excellent predictiveperformanceforCHFhospitalization(C-statistics=0.92).Conclusion:ThecumulativeriskofCHFhospitalizationinACHDissignificantlyhigherthanthatinthegeneralpopulation.CHFhospitalizationisstronglyassociatedwithanincreasedriskofdeathinACHDpopulation.WedevelopedandvalidatedaconvenientclinicalriskscoreforpredictingtheriskofCHFhospitalizationin1year.Itcouldbereadilyappliedatclinicsforidentifyinghigh-riskpatientsofCHFhospitalizationwhoaremostlikelytobenefitfromhighlyspecializedservicesinreducinghospitalizationrisk.KeywordsCongenitalheartdisease,Heartfailure,Mortality,Risk

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#29-ClinicalorPopulationHealthPredicting Electrocardiographic and Echocardiographic Response to CardiacResynchronization Therapy: the Use of Strict Left Bundle Branch BlockCriteria

Ahmed Al Turki, McGill University Health Center; Alexios Hadjis, McGill University Health Center; Riccardo Proietti,SwanseaUniversity;VidalEssebag,McGillUniversityHealthCenter

Background:Cardiacresynchronization therapy(CRT)reducesmorbidityandmortality inheartfailurewithreducedejectionfraction(HFrEF).CRTefficacyisgreaterinpatientswithleftbundlebranchblock(LBBB).ThisstudyaimedtodetermineifstrictLBBBcriteriapredictsanimprovedCRTresponse.Methods: HFrEF patients who received a de novo CRT device at a single tertiary center wereincluded.Patientsweredividedinto3groupsbasedonQRSmorphology.StrictLBBBwasdefinedasmidQRSnotchingorslurringintwoofthefollowingleads(I,aVL,V1,V2,V5,V6),QRS>140msinmenand>130msinwomeninadditiontoconventionalcriteria,definedasQSorrSinV1andamonophasicRwithnoqwavesinI,V6;forconventionalLBBB,theQRShadtobe>120ms.Group1consistedofpatientswithstrictLBBB.Group2hadconventionalLBBBandgroup3hadnon-LBBBmorphology. The primary endpoint was change in QRS duration after CRT. The secondaryendpointswerechangeinEFandthecorrelationbetweenchangeinQRSdurationandchangeinEF.Results: In 204 patients, mean age was 73.1 years, 74% were men and 51% had ischemiccardiomyopathy.Inaddition,74%werehypertensive,38%haddiabetesmellitusand13%hadapreviousstroke.51%ofpatientswereingroup1,27%wereingroup2and22%wereingroup3.The mean change in QRS was -20.7±12.6, +5.2±17.0 and +18.5±28.4 in groups 1, 2 and 3respectively. StrictLBBBpredicteda significant improvement inQRScompared to conventionalLBBB (p

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#34-ClinicalorPopulationHealthArterialstiffnessisabetterearlypredictorforpre-eclampsiathanangiogenicbiomarkersanduterinearteryDopplerultrasound

KimPhan,Yessica-HaydeeGomez,JessicaGorgui,AmiraEl-Messidi,RobertGagnon,StellaDaskalopoulou

Background:Pre-eclampsiaisanimportantcauseofmaternalandfetalmorbidityandmortality,and isassociatedwith increasedrisk for long-termcardiovascularevents.Currently, there isnoearlypredictivetoolforpre-eclampsiainclinicaluse.Methods:Inthisprospectivelongitudinalstudy,womenwithhigh-risksingletonpregnancieswererecruitedandarterialstiffnesswasmeasuredusingapplanationtonometry(SphygmoCor,AtCor)and compared between women who developed pre-eclampsia and those with a normotensivepregnancy. Arterial stiffness and hemodynamics were assessed, in the 1st trimester, every 4weeksthereafter,andat6weekspostpartum.Angiogenicbiomarkersweremeasured(Quantikine,R&D Systems) at each trimester and at six weeks postpartum, and a bilateral uterine arteryDopplerwasperformedinthe2ndtrimester.Results: Of the 155 women recruited, 13 developed pre-eclampsia. Analyses adjusted for bothmaternalageandbodymassindexshowedwomenwhodevelopedpre-eclampsiahaddecreasedwavereflectionstarttimeandincreasedcarotid-femoralpulsewavevelocityinthe1sttrimester,throughout pregnancy, and at 6 weeks post-partum with a carotid-femoral pulse wavevelocity:carotid-radial pulse wave velocity mismatch seen in the 1st and 3rd trimester (all p-values < 0.05). Arterial stiffness (AUC-ROC: 0.80) was a better predictor than angiogenicbiomarkers (AUC-ROC:060;p=0.04)oruterinearteryDoppler(AUC-ROC:0.53p<0.001)andimproveddetectionofpre-eclampsiawhencombinedwithallotherpredictors, includingclinicalcharacteristics (arterial stiffness sensitivity: 79.8% vs other predictor combinations sensitivity:69.2%).Conclusions: Arterial stiffness andwave reflectionwas greater in the 1st trimester, throughoutpregnancy,anddoesnotresolve6weeksafterpregnancyinwomenwhodeveloppre-eclampsia.Agreater central to peripheral arterial stiffness mismatch was also observed in the 1st and 3rdtrimester. Arterial stiffness indices had superior predictive value for pre-eclampsia overangiogenic biomarkers and uterine artery Doppler alone and improved detection rates whencombinedwithallotherpredictorsincludingclinicalcharacteristics.KeywordsArterialstiffness,Pre-eclampsia,Prediction

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#35-ClinicalorPopulationHealthRisks of Incident Cardiovascular disease with High Lipoprotein(a) with andwithoutHighLDL-C-TheFraminghamHeartStudy

MehdiAfshar1,2,JianRong3,4,YangZhan1,2,AllanD.Sniderman1,2,MartinLarson3,5,VasanRamachandran6,7,GeorgeThanassoulis1,2,8 1Department of Medicine, McGill University 2Preventive and Genomic Cardiology, MUHC-RI3NHLBI’s andBostonUniversity’s FraminghamHeart Study 4Department ofBiostatistics,BostonUniversity School ofPublic Health 5Department of Mathematics and Statistics, Boston University 6Department of Epidemiology, BostonUniversity School of Public Health 7Preventive Medicine and Cardiology, Boston University School of Medicine8DepartmentofClinicalEpidemiology,McGillUniversityHealthCenter

Background:Elevated lipoprotein(a)(Lp[a])affects20%of thepopulationandisacausal factorforcardiovascular(CV)disease.WhetherLp(a)confersgreaterriskwhenLDL-Ciselevatedinnotwell-established. We sought to evaluate the CV risks associated with elevated Lp(a) in thepresenceofhighLDL-C.Methods:WeusedprospectivedatafromtheFraminghamHeartStudy(FHS)examinationcycle5(1991-1995). This cohort includes2680participants (median age=54 years, 46%males)withcomplete follow-up at 15 years (n = 392 incident CV events). Lp(a) wasmeasured at baselineusingELISAwithamonoclonalantibodyagainstapo(a), independentof theapo(a) isoformsize.LDL-C was calculated using the Friedwald equation using standard methods. High Lp(a) wasdefinedas>100nM(~80thpercentile)basedonknownepidemiologicalcut-offsforincreasedriskofCVDandhighLDL-Cwasdefinedas~3.37mmol/L.Results:When combined in the samemodel and after adjustment for other known risk factors,highLp(a)andhighLDL-CweresignificantpredictorsofCVD(HighLDL-C:HR1.34;95%CI1.09-1.64,p=0.006;HighLp(a):HR1.31;95%CI1.03-1.66,p=0.026).Acrossthe4groupsofhigh/lowLp(a) andhigh/lowLDL-C, the absolute risks at15yearswere22.6% (highLp(a)/highLDL-C),17.3%(lowLp(a)/highLDL-C),12.7%(highLp(a)/lowLDL-C)and11.5%(lowLp(a)/lowLDL-C).Afteradjustmentforotherriskfactors,hazardratiosforhighLp(a)/highLDL-were1.83(95%CI1.34-2.47, p=0.0001) as compared to low Lp(a)/low LDL-C; 1.57 (95% 1.03-2.49, p=0.04) ascompared to low Lp(a)/high LDL-C and 1.44 (95% CI 1.05-1.97, p=0.02) as compared to lowLp(a)/lowLDL-C.Resultswereunchangedafterfurtheradjustmentforlipidtreatment.Conclusion:PresenceofbothhighLp(a)andhighLDL-Cisassociatedwithahighabsoluterisksofincidentcardiovasculardisease.OurresultssuggestthatindividualswithbothhighLp(a)andhighLDL-Crepresentahighriskgroup thatmaybenefit fromstatin therapy. Lp(a)measurement inindividualswithhighLDL-Cwhodonotmeetcriteriaforstatinsmaybewarranted.KeywordsLipoprotein(a),Cardiovasculardisease,Dyslipidemia,Framingham

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#40-ClinicalorPopulationHealthExposuretoLow-DoseIonizingRadiationfromCardiacProceduresandRiskofMalignancyinAdultswithCongenitalHeartDisease

SarahCohen1,AihuaLiu1,MichelleGurvitz2,LimingGuo1, JudithTherrien1, JayS.Kaufman3,MichalAbrahamowicz3,ArianeJ.Marelli11McGillAdultUnitforCongenitalHeartDiseaseExcellence,Montreal,Québec,Canada2DepartmentofCardiology,andDepartmentofMedicine,BrighamandWomen'sHospital,HarvardMedicalSchool,Boston,Mass,USA.3DepartmentofEpidemiology,Biostatistics,andOccupationalHealth,McGillUniversity,Montreal,Québec,Canada

Background:Adultswith congenital heart disease (ACHD) are exposed to increasingnumber oflow-dose ionizing radiation (LDIR) from cardiac procedures. The prevalence of cancer in thispopulationishighercomparedtothegeneralpopulation.OurobjectivewastodetermineifthereisanassociationbetweenLDIR-exposurefromcardiacproceduresandcancerincidenceinACHDpatients.Method:A cumulative risk cohortwasderived from theQuebecCHDdatabaseand consistedof24,833ACHDaged18-65between1995-2009.Weconductedtime-to-eventanalysestocalculatethecumulativeriskofcancerandtoassessifhighLDIR-exposure(≥6procedures)wasassociatedwith an increased risk of cancer than lowLDIR-exposure (≤1procedure). Propensity score andinverseprobabilityweightingwereusedtoadjustforpotentialconfounderssuchascomorbidities.Furtherweperformedanested case-control study to investigate if LDIR-exposure fromcardiacprocedureswas predictive of cancer using amultivariable logistic regressionmodel. Each casewasmatchedonsex,CHDseverity,ageandcalendartimewith4randomlyselectedcontrols.AlagtimeofoneyearbetweenLDIRexposuresandcancerdiagnosiswasappliedtoallanalyses.Results: In over 250,791 person-years of follow-up, 602 cancer cases were observed (medianage:55.4years).The cumulative riskof cancerby age64was15.3%(95%CI, 14.2-16.5).Breastcancer(34.5%)wasthemostfrequentsiteinwomenandgenitourinary(30.8%)amongmen.Thecumulative cancer-free survival probability was significantly lower in the high LDIR-exposuregroup than the low LDIR-exposure group. High LDIR-exposure was associated with a 2.6-foldincreaseriskofcancer(hazardratio=2.61,95%CI:2.30-2.96)comparingto lowLDIR-exposure.In the nested case-control study, cancer cases hadmore LDIR-related cardiac procedures thancontrols (1,410versus921per1000ACHDpatients,p

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#43-BasicScienceHuman Amniotic Stromal Cells Encapsulated in a Chitosan/Hyaluronic AcidBasedPlatformProliferateandIncreaseCardiacFunctioninaRatMyocardialInfarctionModel

MakhoulG1, YuB2,Ghulam J3, JaiswalPK1, CerrutiM3, SchwertaniA2, CecereR1 1Departments ofExperimentalSurgery,2ExperimentalMedicine,and3ChemicalEngineering,McGillUniversity,Montreal,Canada

Background: Myocardial ischemia can lead to an irreversible injury and an eventual cardiacfailure.Stemcellsstandasoneoftheleadingexperimentaltherapies.Nonetheless,stemcellbasedcardiac repair suffers from theabsenceof an ideal cell typeand lowcellularengraftment rates.Here, we investigated the cardio-protective potential of a novel composite inserting humanamniotic stromal cells (hASCs) ina chitosan/hyaluronicacid (C/HA)basedplatform to increasecellularretentionratesandcombatheartdegeneration.Method:Are-designedC/HAscaffoldmixedwithhASCsinculturewassynthesized.Itsstructuralcharacteristicsweredetermined.Toexamineitscellularpreservation,Alamarbluewasperformedon hASCs encapsulated in the C/HA. The cardiac impact of hASCs + C/HA compositewas thenassessed in an induced myocardial infarction model. Female Lewis rats (n=40) divided into 4groupswere injectedwith either3x105hASCs, C/HA,3x105hASCs+C/HA, or control. Cardiacfunction was assessed with echocardiography and histological analysis was conductedpostmortem.Results:MechanicalcharacterizationoftheC/HAplatformindicatedinatemperaturesweepassaya swiftelastic conversionat40°C.At37°C, thesol-gel transition timeofC/HAoccurredrapidly.AlamarblueassaypresentedanactiveandproliferatinghASCsafter8days inC/HA. Invivo,onweek 5, the groups injected with C/HA and hASCs + C/HA had significantly higher ejectionfraction,fractionalshortening,andleftventricularendsystolicdiameter.Interestingly,thehASCsin the hASCs + C/HA group were abundantly detected 6 weeks after myocardial injection.Immunofluorescence labeling of these encapsulated cells showed a co-expression of cardiacproteinssuchasconnexin43,myosinheavychain,andtroponinT.Labelingadditionallyrevealedtheco-expressionof theKi67proliferativemarker inthe injectedhASCs.Moreover, thehASCs+C/HA composite triggered a significant and massive neovascularization of CD31+ cells at theinfarctionsite.Conclusion: Despite low injected quantities at baseline, our findings showed that the hASCsencapsulated in C/HA were abundantly retained at the infarction site and increased cardiacfunctionalparameters.Moreover, theC/HAplatformprovidedanactivemilieu for thehASCs toproliferate, co-express cardiac proteins, and induce new vessel formation. Thus, this novelcomposite of hASCs encapsulated in a C/HA biological platform is a conceivable candidate thatcouldrestorecardiacfunctionandreduceremodeling.KeywordsHeartfailure,Amnioticstromalcells,Chitosan,Hyaluronicacid

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#59-ClinicalorPopulationHealthSarcopeniaandMortalityafterCardiacTransplantation

LiorBibasMD1,EliSaleh2,SamahAl-KharjiMD1,JessicaChetrit3,LouisMullieMD4,MarceloCantarovichMD5,RenzoCecereMD6,NadiaGiannettiMD1*,JonathanAfilaloMDMSc1,7**Co-seniorauthors1DivisionofCardiology,McGillUniversity, Montreal, QC; 2 Faculty of Medicine, Université de Montréal, Montreal, QC; 3 Department of Cell andMolecular Biology, Concordia University, Montreal, QC; 4 Division of Internal Medicine, McGill University, McGillUniversity,Montreal,QC;5DivisionofNephrology,McGillUniversityHealthCenter,McGillUniversity,Montreal,QC; 6Division of Cardiac Surgery, McGill University Health Center, McGill University, Montreal, QC; 7 Centre for ClinicalEpidemiology,LadyDavisInstitute,JewishGeneralHospital,Montreal,QC.

Background:Psoasmusclearea(PMA)isavalidatedindicatoroffrailtyandsarcopeniathatcanbeeasily measured on abdominal computed tomography (CT) scans. There has yet to be a studyexaminingtheprognosticimpactofsarcopeniainpatientsundergoingcardiactransplantation.Methods: In this retrospective study, pre- andpost-operativeCT scanswere retrieved for adultpatients transplanted between 2000-2015 and followed at the Heart Transplant Clinic of theMcGill University Health Centre. PMA was measured on axial images at the level of the L4vertebraeusing theCoreSlicer software.Outcomesof interestwereascertainedbychart reviewand included long-term mortality and in-hospital major adverse postoperative events (MAPE;definedasmortality,prolongedintubation,stroke,dialysis,mediastinitis,orreoperation).Results:Outof166patientstransplanted,82patientshadatleastoneabdominalCTscanoveranaverage follow-upof3years.ThemedianPMAwas24.7cm2(IQR20.9,30.0) inmen,16.6cm2(IQR14.9,19.1) inwomen,anddecreasedby8-11%fromthe first to the lastavailableCTscan.PatientswithsmallerPMA,definedaslessthanthesex-stratifiedmedian,hadafour-foldincreaseinMAPE (OR4.28; 95%CI 1.18, 15.46) and a trend towards a three-fold increase in long-termmortality(HR3.12;95%CI0.96,10.20).Adjustingforage,sex,BMI,andcardiomyopathyetiology,every1 cm2 increase inPMAwas found tobe significantly associatedwith a17%reduction inMAPE(OR0.83;95%CI0.72,0.96)anda9%reductioninlong-termmortality(HR0.91;95%CI0.83-0.99).Conclusion:SarcopeniaasdefinedbyPMAisassociatedwithahigherriskofmortalityandmajormorbidity after cardiac transplantation. Further studies are needed to define the longitudinalprogressionofsarcopenia in thispopulationand test thevalueofmuscle-building interventionssuchasexerciseandproteinsupplementationtoimproveshort-andlong-termoutcomes.KeywordsCardiactransplantation,Sarcopenia,HeartFailure,Frailty

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#61-ClinicalorPopulationHealthGenome-wideAssociationStudyandReplicationinupto157,107IndividualsIdentifiesaNovelGeneticLocusforAorticStenosis

Hao Yu Chen1,2, Line Dufresne2, Hannah Burr2, Athithan Ambikkumar2, Benjamin Cairns3, Albert Nguyen2, StefanSoderberg4, Robert Clarke3, Mark Lathrop5,6, James C. Engert*1,2,5, George Thanassoulis*1,2 1Division ofExperimentalMedicine,McGillUniversity, Quebec, Canada 2Research Institute of theMcGillUniversityHealth Centre,Quebec,Canada3CancerEpidemiologyUnit,UniversityofOxford,Oxford,UnitedKingdom4PublicHealthandClinicalMedicine,UmeåUniversity,Umeå,Sweden5DepartmentofHumanGenetics,McGillUniversity,Quebec,Canada6McGillUniversityandGenomeQuebecInnovationCentre,Quebec,Canada*co-seniorauthors

Introduction: Aortic stenosis (AS) is themost prevalent valvular disease in thewesternworld,affectingmore thanonemillion individuals inNorthAmerica.At present, only the LPA locus isknowntoconfergeneticrisk.TheidentificationofadditionalgeneticlocicouldinformfuturedrugdevelopmentforAS,adiseaseforwhichthereisnoeffectivemedicaltherapy.Methods: We conducted a genome-wide association study (GWAS) for AS in the GeneticEpidemiology on Adult Health and Aging (GERA) cohort (44,703 individuals; 3,469 AS cases)across 15.3 million genetic variants, adjusted for age and sex. A locus which demonstratedsuggestive evidence of association with AS in GERA (p

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Poster presentations

abstracts

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#1-BasicScienceThe CCR7+ PDGFRa+ Cell Population Is Increased In RegressingAtheroscleroticPlaques

F Dierick, T Ebrahimian, S Simeone, D Simon, V Michaud and S Lehoux Lady Davis Institute for MedicalResearch,McGillUniversity,Montreal,QC,Canada

Introduction:Atherosclerosisischaracterizedbytheaccumulationoflipids,cellsandfibersin the arterial wall. Atherosclerotic plaques form in regions of low blood flow, whereasvessels exposed to high shear stress remain lesion-free. We created a surgical mousemodel, arteriovenous fistula (AVF), which increases blood flow in the brachiocephalicartery(BCA)specifically,withoutalteringserumlipidlevels.Methods&Results:LDLRKOmicewereplacedonahigh-fatdiet(HFD).Controlmiceweresacrificedatweek12. ShamandAVF surgerywasperformedatweek12andmicewerekeptonaHFDforafurther1-4weeks.Wefoundthathighbloodflowisbeneficialandleadstoasignificant~50%regressionofBCAplaquesizeinAVFmicecomparedwithControls,by week 4. We performed flow cytometry to characterize the different cell populationswithin Sham and AVF plaques. At day 7 after surgery, there was no difference inmacrophage (F4/80+) or dendritic cell (CD11c+) content between Sham and AVF.However, we found a significant, 4-fold increase in the total number of CD45-/CCR7+/PDGFRa+cellsintheBCAplaquesofAVFmicevsShams(p

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#2-ClinicalorPopulationHealthDepression as a Predictor of Mortality in Older Adults UndergoingTranscatheterorSurgicalAorticValveReplacement

MatthewAdes(1),LauraDrudi(1,2),RitaMancini(1),AmandaTrnkus(1),JonathanAfilalo(1,3,4)1)CenterforClinical Epidemiology, Lady Davis Institute, Montreal, QC, Canada 2) Division of Vascular Surgery, McGillUniversity,Montreal,QC,Canada3)DivisionofExperimentalMedicine,McGillUniversity,Montreal,QC,Canada4)DivisionofCardiology,JewishGeneralHospital,Montreal,QC,Canada

Background:Theimportanceofdepressionasariskfactorformorbidityandmortalityhasbeen recently investigated in patients with CAD. The objective of this study was toinvestigate the association between depression and mortality in older adults beingconsideredforsurgical(SAVR)ortranscatheter(TAVR)aorticvalvereplacement.Methods: This was a post-hoc analysis of the FRAILTY-AVR prospective cohort studyincluding14centersin3countries.Olderadults≥70yearsundergoingTAVRorSAVRwithor without revascularization were enrolled. The pre-procedural depression assessmentincludedthe15-itemGeriatricDepressionScaleShortForm(GDS-SF)withascore>5beingsuggestiveofdepression.Thepre-proceduralphysical frailtyassessment includedashortphysical performance battery (SPPB), and cognitive impairment was assessed with themini-mentalstatusexam(MMSE).Theoutcomeswereall-causemortalityat1-monthand12-months. Logistic regression was used tomodel 1- and 12-monthmortality against avarietyofclinicalandproceduralpredictorvariables.Finally,thechangesinGDS-SFscoresat6monthswasusedtoestimate12-monthmortalityinamultivariablelogisticregressionmodel.Results: Among 10,010 older adultswith amean age of 81.4±6.4 years, depressionwasonlypre-operativelydiagnosedin8%ofpatients.However,oncescreened,theprevalenceofdepressionwas32%(N=323)inthecohort.Afteradjustingforclinicalandgeriatricriskfactors, depressionwas found topredictmortality at 1-month (OR2.09, 95%CI: 1.14 to3.77)withanattenuatedresponseat12-months(OR1.06,95%CI0.92to1.22).However,worseningGDS-SFscoresat6monthspredicted12-monthmortality(OR2.88,95%CI1.16to 7.84). Some postulatedmechanisms linking depression to adverse cardiac events andmortalityincludeplateletabnormalities,endothelialdysfunction,andinflammation.Conclusion:Depressionwasfoundtobeapredictorof1-monthmortalitywithworseningdepression scores predictive of 12-monthmortality in older adults undergoing TAVR orSAVR.KeywordsDepression, Surgical Aortic Valve Replacement, Transcatheter Aortic Valve Replacement,Frailty

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#3-ClinicalorPopulationHealthInteractionBetweenFrailtyandAccessSiteinOlderAdultsUndergoingTranscatheterAorticValveReplacement

LauraM.Drudi(a,b),MatthewAdes(a),RitaMancini(a),MelissaBendayan(a,c),AmandaTrnkus(a),DanielI.Obrand (b), Oren K. Steinmetz (b), Jonathan Afilalo (a,d) a Center for Clinical Epidemiology, Lady DavisInstitute, Montreal, QC, Canada b Division of Vascular Surgery, McGill University, Montreal, QC, Canada cDepartmentofExperimentalMedicine,McGillUniversity,Montreal,QC,CanadadDivisionofCardiology,JewishGeneralHospital,Montreal,QC,Canada

Background: Frailty can predict outcomes and guide therapy in older adults beingconsideredfortranscatheter(TAVR).Non-femoralTAVRproceduresaremoreinvasiveandimpart a greater risk of morbidity and mortality compared to trans-femoral TAVRprocedures.Wesoughttoexploreiffrailolderadultsmaybelesscapableoftoleratingtheoperative stress associated with non-femoral transcatheter aortic valve replacement(TAVR)and faceahigherrelativeriskof30-dayand12-monthmortalityascomparedtotheirnon-frailcounterparts.Methods:ThisstudywasaposthocanalysisoftheFRAILTY-AVRprospectivemulticentercohortthatconsistedofolderadultsundergoingTAVRfrom2012-2015.Interactiontablesand multivariable logistic regression models were used to investigate the relationshipbetweenphysicalfrailtyandaccesssiteonourendpointsof30-dayand12-monthall-causemortality.Frailtywasassessedusingtheshortphysicalperformancebattery(SPPB).Effectmodificationwascalculatedontheadditiveandmultiplicativescales.Results:Thecohortconsistedof638patientswithameanageof84±6years,ofwhich492(77%)hadfemoralaccessand146(23%)hadnon-femoralaccess.InfrailpatientswithlowSPPBscores≤5(42%),non-femoralaccesswasassociatedwithincreased30-daymortality(OR3.69,95%CI1.37to10.00);whereasinnon-frailpatientswithSPPBscores>5(58%),non-femoral accesshadno effect (OR0.94, 95%CI 0.21 to3.49). Therewas evidenceofeffectmodificationbetweenfrailtyandTAVRaccesssiteontheadditivescale(RERI=2.56)anda trendon themultiplicativescale (adjustedOR2.42,95%CI0.55 to11.95).Resultswereslightlyattenuatedfor12-monthmortality.Conclusions:Theriskofmortalityisnearly3-foldhigherwhenphysicallyfrailolderadultsundergoaTAVRprocedureviaanon-femoralaccessroute,whilemorerobustolderadultstoleratetheprocedureirrespectiveofaccessroute.KeywordsFrailty,Transcatheraorticvalvereplacement,Peripheralarterialdisease,Access

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#4-ClinicalorPopulationHealthPredictiveImpactofOperativeTimeonMortalityandMajorMorbidityinFrailPatientsUndergoingCoronaryArteryBypassGrafting

JonathanAfilalo, JewishGeneralHospital,McGillUniversity LaurianneRitaGarabed,DepartmentofMedicine,McGillUniversity

Background: Frailtyhasbecomean emergingpublic heath concern in the cardiovascularpopulation, considering that frailty and cardiovascular disease share an overlappingpathophysiology involving common inflammatory markers. Frailty is defined as asyndrome of diminished physiological reserve and increased vulnerability to stressors,such as cardiac surgery. The goal of this study is to determine whether increases inoperativetimeincoronaryarterybypassgrafting(CABG)haveamorenegativepredictiveimpactonpost-operativeoutcomesinfrailpatientscomparedtonon-frailpatients.Itwassoughttocorrelateoperativetimewithincidenceofcomplications30daysand1yearpost-CABG.Studydesign:Thisstudy isapost-hocanalysisofaprospectivemulticentercohortstudy,based on the Prospective Frailty-ABCs Longitudinal Frailty Registry. The exposure –operativetime–wassetascardiopulmonarybypasstime(CPBT).Primaryoutcomesweremergedintoasinglecompositeendpoint–MAPE(majoradversepost-operativeevent)–whichincludedall-causemortalityaswellasmajormorbiditywithin30days.Mortality12months post-opwas included as a secondary endpoint. Logistic regressionmodelswereusedtostudythe interactionbetweenCPBTandoutcomes.ModelswereadjustedfortheSociety of Thoracic Surgeons (STS) predicted risk ofmortality. Statistical analyseswereperformedusingtheSTATAsoftwarepackage.Results:Datawereanalyzed from403and337patientsat30daysand1-year follow-uprespectively. Itwas found that 31.7% of frail patients, in contrast to 17.9% of non-frail,endedupwithaMAPEafter30days.Outcomeswerealsoworsefor frailpatientsafter1year.CPBTwasfoundtobeanegativepredictorofMAPEinbothfrailandnon-frailpatients(OR=1.02foreachadditionalminute,p

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#5-BasicScienceMechanobiologyofintracranialaneurysms:Anovelinvitromodel

CampeauMA1,LeaskRL1.1DepartmentofChemicalEngineering,McGillUniversity,Montreal,QC

An intracranial aneurysm (IA) is a serious health concern as its spontaneous rupture isassociated with catastrophic outcomes and fatality. Despite recent advances, ourunderstanding of what causes IA is limited. On one hand, medial imaging andcomputational fluid dynamic analysis have shed light on the specific flow patternsoccurring inside IAs without clearly identifying hemodynamic factors responsible forrupture. On the other hand, animal models have shown evidences of the implication ofhemodynamics and inflammation in the process of vascular remolding but lack fromcontrolledflowconditionsandcharacterizationoftheendothelialcell(EC)signaling.ECs,beingthecellsincontactwithbloodflow,convertmechanicalstimulitointra/intercellularbiochemical signals, a process known as mechanotransduction. This normally balancedregulationcanbedisruptedbyaberranthemodynamics.Therefore,itishypothesizedthatfocalexposuretoaberrant levelofwallshearstress(WSS)inthevicinityofIAdrivesthepathologicaloutwardvascular remodeling. Ageometrically realistic invitro cell culturemodelbasedonrealpatientdimensionswasdeveloped.Numericalflowsimulationswereused todefine IA typical flowpatterns for themodelgeometries.Threegeometriesweredesigned to represent the gradual vascular remodeling occurring at the apex of abifurcation artery. A novel sugar casting method along with 3D printing allowed thecreation of phantom models with complex shapes. These models consist in a tubular-shaped negative geometry, representing the lumen of an artery, embedded in a matrixmaterial,polydimethylsiloxane.HumanaorticECswere cultured in themodels to formamonolayer before being exposed to physiologically relevant level of WSS. PreliminaryresultshaveshownevidenceofsuccessfulcellcultureoftheECsandtheirresponsetoflow.ImmunofluorescenceimagingofF-actinhasshownthedifferentialadaptationofECsintheregions of themodels (inlet, apex, outlet). Similarly, VE-Cadherinwas expressed by ECsthroughoutthemodel,showingcell-celljunctions,anhallmarkofaformedcellmonolayer.Conclusion. Novel IA phantom models suitable for the characterization of ECsmechanobiology have been developed and will be used for further characterization ofbiomarkersinvolvedinIApathology.KeywordsIntracranial aneurysm, Realistic in vitro model, Mechanobiology, Wall shear stress,Vascularremodeling

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#6-ClinicalorPopulationHealthRisk of Stroke and Major Bleeding Associated with Anticoagulation inPatientswithAtrialFibrillationandAdvancedChronicKidneyDisease

Michelle Samuel MPH(1), Jacqueline Joza MD(2), Hassan Behlouli PhD(1), Vidal Essebag MD PhD FHRS (2),LouisePiloteMDPhDMPH(1)(1)ResearchInstituteofMcGillUniversityHealthCentre,DepartmentofClinicalEpidemiology(2)ResearchInstituteofMcGillUniversityHealthCentre,DivisionofCardiology

Background: Chronic kidney disease (CKD) is an independent risk factor for stroke inpatients with atrial fibrillation (AF). The management of oral anticoagulation (OAC) isparticularly difficult in this population as warfarin is associated with a significantlyincreasedriskofbleeding. Inanattempt tobalancestrokeandbleedingrisks,directoralanticoagulants(DOACs)havebeenuseddespitelimiteddata.OBJECTIVE:ToevaluatetheriskofstrokeandmajorbleedingassociatedwithuseofDOACsandwarfarininAFpatientswithadvancedCKD.Methods:Apopulation-basedcohortwasconstructedofAFpatientswithstageIIIbtostageVCKD from theMarketScanResearchDatabase (2005-2009).Patientswitha glomerularfiltrationrate(GFR)of

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#7-ClinicalorPopulationHealthCOasthebestpredictorinTetralogyFallotpatients.IsCOtherootofthestory?

MariaOrdoñez,ArianeMarelli,LucJutras,TherrienJudith.

Background: Cardiac index (CI) was shown to be the best predictor to cardiachospitalization and cardiac interventions in patients with congenital heart disease.However, it has not been studied specifically in patientswith Tetrallogy of Fallot (TOF).Thegoalofour study,was to see ifCIdiffered inTOFpatientswithandwithout clinicaldeterioration.Methods: Patients with TOF who underwent a transannular patch repair with residualseverepulmonary regurgitation (PR)were enrolled in this study. CIwasmeasured fromtheir first cardiac magnetic resonance imaging (MRI) study performed as an adult andclinical chartswere reviewed for any clinical outcome including 1) ]the development ofarrhythmias,syncope,suddendeath,worseningNYHAclassoradmissionforheartfailure.Results: 82 patients (52%male)were included in the study.Mean age atMRIwas 20,5yearsandmeanfollowwas5years.Twentytwopatients(27%)developedoutcomes.SVTin 13 patients, VT in 6 patients, SCD in 3 patients andworsening NYHA in 18 patients.Patient with clinical outcome had a CI of X compared to Y in the no cardiac outcome(p=0,06) . The lower the CI, the more the outcomes. There was also a non significantinverserelationshipbetweentheCIandtheburdenofoutcome.Conclusions: CI in patients with TOF repair and residual severe PRmay predict clinicaloutcome.Pediatricpatientswillbeincludedinournextanalysistoincreaseournumbers.KeywordsTetralogyofFallot,Cardiacindex,Longtermoutcomes

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#8-ClinicalorPopulationHealthEfficacyandSafetyofSmokingCessationInterventionsinPatientsWithCardiovascular Disease: A Network Meta-Analysis of RandomizedControlledTrials

Karine Suissa, Jordan Lariviere, Mark J. Eisenberg, Maria Eberg, Genevieve C. Gore, Roland Grad, LawrenceJoseph,PaulineReynier,KristianB.Filion.

Background:Althoughtheefficacyandsafetyofsmokingcessationinterventionsarewellestablished,theirefficacyandsafetyinpatientswithcardiovasculardisease(CVD)remainunclear. The objective of this study was to evaluate the efficacy and safety ofpharmacological and behavioral smoking cessation interventions in CVD patients via ameta-analysisofrandomizedcontrolledtrials.Methods: EMBASE, PsycINFO, MEDLINE, PubMed, and the Cochrane Tobacco AddictionSpecializedRegisterweresearchedforrandomizedcontrolledtrialsevaluatingtheefficacyof smoking cessation pharmacotherapies and behavioral therapies in CVD patients.Outcomesofinterestweresmokingabstinenceat6and12months,definedusingthemostrigorous criteria reported.Datawerepooledacross studies fordirect comparisonsusingrandom-effects models. Network meta-analysis using a graph-theoretical approach wasusedtogeneratetheindirectcomparisons.Results:Sevenpharmacotherapyrandomizedcontrolledtrials(n=2809)and17behavioralintervention randomized controlled trials (n=4666) met our inclusion criteria. Ournetworkmeta-analysisrevealedthatvarenicline(relativerisk[RR]:2.64;95%confidenceinterval[CI],1.34-5.21)andbupropion(RR:1.42;95%CI,1.01-2.01)wereassociatedwithgreaterabstinence thanplacebo.Theevidenceaboutnicotine replacement therapieswasinconclusive (RR: 1.22; 95% CI, 0.72-2.06). Telephone therapy (RR: 1.47; 95% CI: 1.15-1.88)andindividualcounseling(RR:1.64,95%CI:1.17-2.28)werebothmoreefficaciousthanusualcare,whereasin-hospitalbehavioralinterventionswerenot(RR:1.05;95%CI,0.78-1.43).Conclusions:Ourmeta-analysis suggestsvareniclineandbupropion,aswellas individualandtelephonecounseling,areefficaciousforsmokingcessationinCVDpatients.KeywordsBehaviortherapy,Bupropion,Cardiovasculardisease,Meta-analysis,Smoking,Tobaccousecessationproducts,Varenicline

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#9-BasicScienceRole of the inflammasome in angiotensin II-induced hypertension andvascularinjury

Dancose-Giambattisto B1, Caillon A1, Fraulob-Aquino JC 1, Coelho SC1, Paradis P1 and Schiffrin EL1,21Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research and 2Department ofMedicine,SirMortimerB.Davis-JewishGeneralHospital,McGillUniversity,Montréal,Quebec,Canada

Background:Innateimmunecells(monocyte/macrophages)andadaptiveimmunecells(Tlymphocytes) play an important role in the development of vascular lesions inhypertension.Innateimmunecellsplayaroleintheinitiationandsubsequentdirectionofthe adaptive immune response, mechanisms that could also occur in hypertension andvascular injury. Inhypertension, thiscross-talkmightbe initiated in innate immunecellsviaactivationof caspase-1by theNLRP3 inflammasome, and followedby releaseofpro-inflammatorycytokines suchas interleukin (IL)-1b,whichwill activateadaptive immunecells.However,itisunclearwhetherNLRP3playsaroleinvascularinjuryinhypertension.We hypothesized that Nlrp3 knockout would prevent angiotensin (Ang) II-inducedhypertensionandvascularinjury.Methods:NLRP3knockout (Nlrp3-/-)andwild-type (WT)micewere infusedwithAng II(490 ng/kg/min, SC) for 14 days. Systolic blood pressure (SBP) was measured bytelemetry,andsmallmesentericartery(MA)endothelialfunctionandvascularremodelingbypressurizedmyography.Spleenmonocyteprofilewasassessedbyflowcytometry.Results:After14daysoftreatment,AngIIincreasedSBPby43mmHginWTmice,whichwas unaffected byNlrp3 knockout. Endothelium-dependent acetylcholine relaxationwasdecreased by ~40% in the mesenteric arteries of Ang II-infusedWTmice compared tocontrol.ThiseffectwasabrogatedinNlrp3-/-mice(P

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#10-BasicScienceInduction of human endothelin-1 overexpression for 3 months causesblood pressure rise and small artery endothelial dysfunction andstiffening

Suellen C. Coelho1, Olga Berillo1, Sofiane Ouerd1, Júlio C. Fraulob-Aquino1, Stefan Offermanns3,4, PierreParadis1, ErnestoL. Schiffrin1,2 1VascularandHypertensionResearchUnit, LadyDavis Institute forMedicalResearch and 2Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University,Montréal, Canada. 3Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, BadNauheim,Germany4MedicalFaculty,J.W.GoetheUniversityFrankfurt,Frankfurt,Germany

Background:Mechanismsofbloodpressure(BP)regulationbyendothelin(ET)-1producedby endothelial cells are complex and remain unclear. We have previously shown thattamoxifen-inducible endothelium-restricted human ET-1 overexpression (ieET-1) miceexhibitedBPriseafter3weeksof inductioninanETtypeAreceptor(ETAR)-dependentmanner, in absence of vascular injury. It is unknown if long-term exposure to ET-1overexpressionresultsinsustainedBPelevationandvascularinjury.Methods:Nineto12-weekoldmaleieET-1andcontrolieCremiceexpressingatamoxifen-inducibleCrerecombinaseintheendotheliumweretreatedwithtamoxifen(1mg/kg/day,s.c.) for 5 days and studied 3months later. ieET-1micewere treated or notwith ETARblocker,atrasentan(10mg/kg/day,PO)inthelast2weeksofthestudy.BPbytelemetry,mesenteric artery (MA) endothelial function and vascular remodeling determined bymyography,reactiveoxygenspecies(ROS)generationusingdihydroethidiumstaining,andimmune cell infiltration by immunofluorescence in MA or perivascular fat (PVAT) weredeterminedattheendofthestudy.Results:SystolicBPincreased27mmHginieET-1comparedwithieCre(P

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#11-ClinicalorPopulationHealthTreatment-induced diastolic hypotension attenuates benefits frombloodpressurecontrol

Todd C. LeeMDMPH (McGill) Rodrigo B. CavalcantiMDMSc (Univ. Toronto) Emily G.McDonaldMDMSc(McGill)LouisePiloteMDMPHPhD(McGill)JamesM.BrophyMDPhD(McGill)

Background:TheSystolicBloodPressureInterventionTrial(SPRINT)concludedthatintensivesystolicbloodpressure (SBP) lowering to≤120mmHg,as comparedwithstandard treatmenttargets of ≤140mmHg,was associatedwith lower rates of fatal and non-fatal cardiovascularevents.AsexcessiveloweringofDBPmaycauseharm,wereanalyzedSPRINTdatafocusingontreatmentinduceddiastolichypotension,andtheprimarycompositeoutcome,ordeath.Methods:Diastolichypotensionwasdefinedas≤55mmHgasSPRINTautomatedBPestimatesyield values at least 5-10mmHgbelow standardofficemeasurements.We excludedpatientswithout follow-upvisits,withmissingdataon theprimaryoutcome,orwith incompletedataforaspirinandstatinuse.Wefurtherrestrictedouranalysistospecificallyaddresstreatment-induced diastolic hypotension. We performed a multivariable cox-proportional hazardsanalysis to evaluate the effects of diastolic hypotension on the composite primary outcome(myocardial infarction, other acute coronary syndromes, stroke, heart failure or death fromcardiovascular causes), or all cause death. To avoid misclassification of exposure,DBP≤55mmHgwasmodelledasatime-dependentcovariate.Results:Onmultivariableanalysis,among7977patients(4009interventionand3968control),treatmentofhypertensionleadingtoaDBP≤55mmHgwasassociatedwithanincreasedriskfor the primary outcome or death (HR 1.68; 1.25-2.27, p=0.001). This was true both forparticipants randomized to intensive (HR 1.55; 1.05-2.28, p=0.028) and standard treatment(HR2.21; 1.39-3.52, p=0.001),withno statistically significant interaction (p=0.098)betweendiastolichypotensionandtreatmentstrategyallocation.Discussion:InreanalyzingSPRINT,weconfirmedthattreatmentinduceddiastolichypotensionis associated with an increased risk of combined cardiovascular morbidity and mortality.Despite similar hazard ratios between intensive and standard-treatment groups, the rate ofdiastolichypotensionwasmorethanthreetimeshigherwith intensivetherapy.Althoughtherandomized design of SPRINT suggests that the association between treatment strategy andlowDBPiscausal,itisnotclearthatlowDBPhasadirectcausaleffectonadverseoutcomesorif it is merely a marker of overall frailty or poor health. Nonetheless, targeting a SBP of≤120mmHg is now being incorporated into practice guidelines, possibly without adequateconsiderationoftheunintendedconsequencesofexcessiveDBPlowering.Conclusion:Apost-hocanalysisofSPRINTtrialdatasuggeststhattreatment-induceddiastolichypotension may lead to harm, potentially counteracting benefits associated with intensiveSBP lowering. RegardlessofSBP target, ifmaybeadvisable tomaintainanadequateDBP inordertomaximizecardiovascularoutcomes.

KeywordsDataparasites,Hypertension,HighvalueHealthcare,Overtreatment

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#12-ClinicalorPopulationHealthFrailty is Associated with Baseline Functional Limitation and 1-YearMortality in Older Adults Undergoing Transcatheter Aortic ValveReplacement

MinaGirgis,MD;JonathanAfilalo,MD,MSc.McGillUniversity,Montreal,Canada

Background:NewYorkHeartAssociation(NYHA)class isacriticalmeasureof functionalstatus and prognosis in patients with severe aortic stenosis (AS) being considered fortranscatheter aortic valve replacement (TAVR). These patients are affected by multiplecomorbid conditions such that the drivers of NYHA class are multi-dimensional andincompletely understood. We evaluated the correlates of baseline NYHA class in thispopulation,anddeterminedwhichoftheseNYHAcorrelateswerepredictiveofsubsequentmortalityafterTAVR.Methods:TheFrailty-AVRcohortstudyprospectivelyenrolledolderadultswithsevereASundergoing TAVR between 2012-2015 at 14 centers in 3 countries. NYHA class wasascertained at baseline along with comorbid conditions and echochardiographicparameters. Physical frailty was quantified with the short physical performance battery(SPPB)thatisscored0-12basedon5-metergaitspeed,timedchairrises,andbalance.Theprimaryoutcomewasall-causemortalityafter1yearoffollowuppost-TAVR.Results:Among621patients,withanaverageageof84±6yearsand46%females,70%hadabaselineNYHAclassof3or4.MultivariablelogisticregressionshowedthatNYHAclasswas associated with: frailty, obesity, lung disease, aortic valve area, and left ventricularejectionfraction.ThefollowingwerenotsignificantlyassociatedwithbaselineNYHAclass:age, sex, mean aortic gradient, peripheral arterial disease, coronary artery disease, andatrial fibrillation.Of theNYHA correlates, frailtywasmostpredictiveof 1-yearmortalitywithanoddsratio(OR)forSPPB≤5of4.17(95%CI2.16,8.04)andforSPPB6-8of2.79(95%CI1.39,5.57).Oxygen-dependentlungdiseasewasalsopredictiveof1-yearmortality(OR3.11;95%CI1.10,8.79)whereasobesityhadaprotectiveeffect(OR0.54;95%CI0.30,0.95).Conclusion:Physical frailty is stronglyassociatedwithNYHA limitationandpredictiveofmid-term mortality in older adults with severe AS undergoing TAVR. Other factorsassociatedwithNYHAlimitationarechroniclungdisease,ASseverity,andleftventriculardysfunction. Obesity is associated with NYHA limitation but, paradoxically, predictiveagainstmid-termmortality.KeywordsNYHA,Frailty,TAVR,Aorticstenosis,SPPB

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#13-ClinicalorPopulationHealthVariabilityinHigh-SensitivityCardiacTroponinTinPatientswithStableCoronaryArteryDisease

JamesBrophyMDPhD,PeterBogatyMD,GillesDagenaisMDDivisionsofCardiology,McGillUniversity&LavalUniversity

Background:Increaseofhigh-sensitivitycardiactroponin(hs-cTn)Tabovetheupper99thpercentile is the diagnostic cutoff for acute myocardial infarction without knowing itsvariability in stable patients with different coronary artery disease (CAD) history. Weassessedhs-cTnTvariabilityinsuchpatients.Methods:Weprospectivelystudied4groupsof25stablesubjects(aged64,83%men):1)recurrent acute coronary syndrome (ACS) with last event > 3 months; 2) a singlemyocardialinfarction(MI)≥7yearsandnootherCAD;3)CADwithoutanypreviousACS;4) no angiographic evidence of CAD. Hs-cTnT was obtained 3 times during one day; 5consecutivedays;4consecutiveweeks;4consecutivemonths;andevery3monthsovertheyear. Variability and contributing factorswere assessed usingmultivariate analyses andhierarchy models. Each patient therefore had a possible 15 measurements which weretaken exclusively during clinical quiescence. All hs-cTnTmeasurementswere performedsimultaneouslyonanautomatedplatformmodularanalyticsE170usingahighlysensitiveimmunoassay(TroponinThsRocheDiagnostics).AlldataexploratoryanalysesandmixedlinearmodelingwasperformedinR.Results: In1491hs-cTnTsamples fromthe100participants,103(6.9%)wereabove theconventionalacuteMIthresholdof14ng/L.Amongthe75stableCADpatients9.1%ofthe1116hs-cTnTmeasurementswere>14ng/lwas9.1%whileonly0.5%ofthe375hs-cTnTmeasurementsinthe25stablepatientswere>14ng/lwas0.5%.Intherecurrentgroup,66ofthe370samples(17.8%)wereabove14ng/l.Otherindependentfactorsassociatedwith increased hs-cTnT measurements were diabetes (p

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#17-ClinicalorPopulationHealthEchocardiographicmid-ventricularlineardimensionsaremoreaccuratethantraditionalbasal-levellineardimensions:AnMRIvalidationstudy

Michael Chetrit M.D.1, Logan Timmins., Sebastien Roujol Ph.D3 , Robert A. Levine M.D. 2 Arthur E.WeymanM.D.2,AidanW.FlynnM.D.Ph.D.2DavidM.ShahianM.D.2,MichaelH.Picard,M.D.2,JonathanAfilaloM.D.MsC1.1JewishGeneralHospital,McGillUniversity,QcCanada;2MassacheusetsGeneralHospital,HarvardUniversity,BostonMA;3KingscollegeLondon,LondonEngland

Background: Echocardiographic assessment of left ventricular (LV) size begins with thesimple measurement of linear dimensions that approximate its volume based on theellipsoidmodel.Oneofthefundamentallimitationsisthatlineardimensionsare-basedonantiquatedconventions-measuredatthebasalleveloftheLVthatdoesnotrepresentthetruediameteroftheellipsoid.ObjectiveTheobjectiveofthisstudywastodeterminetheoptimal level tomeasuretheLVcavitydiameterandwall thicknesswhichwouldprovidethemostaccurateestimateofLVend-diastolicandend-systolicvolumes(LVEDV,LVESV),LVmass(LVM),andLVejectionfraction(LVEF).Methods and Results: To determine the optimal level to measure linear dimensions, aderivationcohortof75patientshavingundergoneaclinically-indicatedcardiacMRIattheJewish General Hospital was assembled. Patients had ischemic heart disease (N=25),nonischemic cardiomyopathy (N=25), or no structural heart disease (N=25). The 3-chamber viewwas analyzedusing a customMATLABprogram tomeasure the LV cavitydiameter andwall thickness at 15 equidistant levels from base to apex. The volumetricestimatesderivedfromeachoftheselevelswascomparedagainstthemethodofdiscsfromtheshort-axisstack(referencestandard).TheoptimallevelwasfoundtobethemidLVattheinflectionpointoftheseptum,havingastrongercorrelationwiththemethodofdiscsthanthebasalLVforLVEF(R0.83vs.0.78),LVEDV(R0.86vs.0.84),andLVM(R0.83vs.0.80), A validation cohort of 100 patients having undergone a clinically-indicatedechocardiogrambeforecardiacsurgerywasextracted fromthePOSSEstudy.ThemidLVcavitydiameteryieldedastrongercorrelationwiththemethodofdiscsthanthebasalLVcavitydiameterforLVEF(R0.96vs.0.80)andLVESV(R0.90vs.0.86).Conclusion:MeasurementofLVdimensionsattheoptimalmid-ventricularlevelprovidesamore accurate estimate of LV size and function as compared to the traditionallyrecommendedbasallevel.Inparticular,calculationofLVEFbasedonmeasurementsatthemid-ventricular level appears to bemore robust and less vulnerable to sigmoid septumvariantsorregionalwallmotionanomalies.KeywordsLinearDimensions,Echocardiography,EjectionFraction,Teicholtz

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#18-BasicScienceEndothelin-1 exaggerates type-1 diabetes-accelerated atherosclerosisthroughnadphoxidases1and4

Sofiane Ouerd1, Noureddine Idris-Khodja1,Michelle Trindade3, Suellen C. Coelho1,Mario F. Neves3, Karin A.Jandeleit-Dahm4, Pierre Paradis1, Ernesto L. Schiffrin1,2 1Hypertension and Vascular Research Unit, LadyDavis Institute for Medical Research and 2Department of Medicine, Sir Mortimer B. Davis-Jewish GeneralHospital,McGillUniversity,Montréal,Quebec,Canada;3DepartmentofClinicalMedicine,StateUniversityofRiodeJaneiro,RiodeJaneiro,Brazil;4BakerIDIHeart&DiabetesResearchInstitute,Melbourne,Australia.

Objective:NADPHoxidase(NOX)1butnotNOX4-dependentoxidativestressplaysaroleindiabeticvasculardisease,includingatherosclerosis.Endothelin(ET)-1hasbeenimplicatedindiabetes-inducedvascularcomplications.WeshowedthatcrossingmiceoverexpressingET-1 selectively in endothelium (eET-1)with apolipoprotein E knockout (Apoe-/-)miceexaggeratedhigh-fatdiet-inducedatherosclerosisinpartbyincreasingoxidativestress.Wehypothesized that ET-1 overexpression in the endothelium would exaggerate diabetes-acceleratedatherosclerosisthroughamechanisminvolvingNOX1butnotNOX4.Method:Six-week-oldmaleApoe-/-mice,eET-1/Apoe-/-andeET-1/Apoe-/-micedeficientin Nox1 (eET-1/Apoe-/-/Nox1y/-) or Nox4 (eET-1/Apoe-/-/Nox4-/-) were rendereddiabeticwith55mg/kg/daystreptozotocin (STZ) IP injections for5daysandstudied14weeks later. Endothelial function and vascular remodeling were assessed in mesentericarteries(MA)usingpressurizedmyography.AorticatheroscleroticlesionswerequantifiedusingOilRedOstaining.Plasmacholesterol,HDLandtriglyceridesweremeasured.Results: Diabetic Apoe-/- mice presented an impaired endothelium-dependentvasodilatoryresponsetoacetylcholine,whichwasnotobservedindiabeticeET-1/Apoe-/-,eET-1/Apoe-/-/Nox1y/-oreET-1/Apoe-/-/Nox4-/-mice(Emax:20±6vs99±1,98±1and100±0%).ET-1overexpressioncauseda1.8-foldincreaseinMAmedia/lumenofdiabeticApoe-/- mice (5.3±0.3 vs 2.9±0.2%), which was further increased 1.2-fold by Nox4(6.4±0.3%)butnotNox1knockout (5.5±0.3%).ET-1overexpressionexaggerated>2-foldthe atherosclerotic lesion area in the aortic sinus in diabetic Apoe-/-mice (plaque area[x105µm2]:5.3±0.5vs2.9±0.6),whichwas reduced~40%byNox1andNox4knockout(plaque area [x105 µm2]: 3.3±0.6 and 3.6±0.6). Plasma triglycerideswere unaffected byET-1overexpressionbutreducedbyNox1(2.2±0.4vs3.4±0.3mmol/L)andNox4knockout(1.8±0.4mmol/L).PlasmaHDLandcholesterolweresimilarbetweengroups.Conclusions: Increased levels of ET-1 exaggerate diabetes-accelerated atherosclerosisthrough NOX1 and NOX4, despite paradoxically improving endothelium-dependentrelaxationinsmallarteries.KeywordsDiabetes,Endothelin-1,NADPHoxidaseisoforms,Atherosclerosis,Vascularinjury

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#19-ClinicalorPopulationHealthOptimal Timing of Complete Revascularization in Acute CoronarySyndrome:ASystematicReviewandMeta-Analysis

RouanGaffar*†,BettinaHabibMScMScPH*,KristianB.FilionPhD*†‡§,PaulineReynierMSc*,MarkJ.EisenbergMD MPH*†‡|| *Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGillUniversity, Montreal, QC †Faculty of Medicine, McGill University, Montreal, QC, Canada ‡Department ofEpidemiology,BiostatisticsandOccupationalHealth,McGillUniversity,Montreal,QC§DepartmentofMedicine,McGillUniversity,Montreal,QC ||Division of Cardiology, JewishGeneralHospital/McGillUniversity,Montreal,QC,Canada

Background:Previousstudieshavesuggested thatcomplete revascularization is superiorto culprit-only revascularization for the treatment of enzyme-positive acute coronarysyndrome (ACS). However, the optimal timing of a complete revascularization strategyremains unclear. We conducted a systematic review and meta-analysis of randomizedcontrolled trials (RCTs)comparingsingle-stagecomplete revascularization tomulti-stagepercutaneous coronary intervention (PCI) in ST-segment elevationmyocardial infarction(STEMI)ornon-STEMIpatientswithmulti-vesseldisease.Methods:We systematically searched theCochraneCentralRegister of ControlledTrials,EMBASE, PubMed, and Medline for RCTs comparing single-stage completerevascularization to multi-stage revascularization in enzyme-positive ACS patients. Theprimary outcome was the incidence of major adverse cardiovascular events (MACE) atlongestfollow-up.DatawerepooledusingDerSimonianandLairdrandom-effectsmodels.Results: Four RCTs (n=838) were included in our meta-analysis. The risk of unplannedrepeat revascularization at longest follow-up was significantly lower in patientsrandomized to single-stage compared to multi-stage revascularization (risk ratio [RR]:0.68; 95%CI: 0.47, 0.99). Results also suggest a trend towards lower risks ofMACE forpatientsrandomizedtosingle-stagerevascularizationat6months(RR:0.67;95%CI:0.40,1.11) and at longest follow-up (RR: 0.79; 95% CI: 0.52, 1.20). Risks of all-cause andcardiovascularmortalityandrecurrentMIatlongestfollow-upwerealsolowerwithsingle-stagerevascularization,but95%CIswerewideandincludedthenull.Conclusion: Single-stage complete revascularization is safe and may have a protectiveeffect against MACE in the long-term, which appears to be driven by a lower risk ofunplannedrepeatrevascularization.KeywordsPercutaneouscoronaryintervention,Completerevascularization,Stagedrevascularization,Acutecoronarysyndrome,Meta-analysis

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#20-ClinicalorPopulationHealthUsingtransesophagealechostrainimaginingtomeasurethemechanicalstateofascendingaorticaneurysms

Emmott,A.*,1,2,Alzahrani,H.3,Alreishidan,M.3,Lachapelle,K.3,Leask,R.L.1,2AuthorAffiliation*PresentingAuthor 1-Department of Chemical Engineering, McGill University, Montreal, QC, Canada 2-Research Centre,Montreal Heart Institute, Montreal, QC, Canada 3-Department of Surgery, Royal Victoria Hospital, McGillUniversity,Montreal,QC,Canada

Background:Aneurysmsof theascendingaorta(AA),at largediameters, require invasiveprophylacticsurgerytoguardagainstthedeadlyriskofaorticwallruptureordissection.Current clinical guidelines recommend resection of AA aneurysms at diameters ≥5.5cm;however,~40%of all AA dissections occur below this threshold. Here,we propose thatusingpre-operativetransesophagealechocardiography(TEE)strainimagingwithparallelbloodpressuremeasurementscanreveal themechanical stateof theaorticwall, therebyhighlightingitspotentialuseinsurgicaldecision-making.Methods: Echocardiography-A total of 18 patients undergoing aortic resection wererecruitedwithconsenttoparticipateinthisstudy.Atthetimeofsurgery,beforethepatientwasputoncardiopulmonarybypass,TEEimaging(GEVivid7)oftheaorticshort-axisandinvasiveradialbloodpressuretracesweretakenfor3cardiaccycles.UsingEchoPac™andpost-processinginMatlab™,circumferentialstretchprofilesweregeneratedfromtheechoprofile and combinedwith the blood pressure traces. From this data, two novel in vivostiffnessmoduliweredeveloped.Exvivobiomechanics-foreachpatient,aspecimenoftheresected aortic ring was clipped for orientation and stored in saline. Four 1.5x1.5cm2testing squares were isolated at even intervals around the aortic circumference. Eachsquareunderwentequibiaxialtensiletestingat37°Ctogeneratestress-stretchprofilesforeach patient. Two parameters were calculated from these profiles: aortic stiffness andenergy loss. Samples of the aortic wall were processed for histological staining usingMovat’spentachrome.Results: Invivoaorticdiameter isonlyweaklypredictiveof exvivoaorticbiomechanics.The novel stiffness moduli derived from TEE imaging demonstrate strong, positivesignificant covariancewith ex vivo tensile biomechanical indices, including stiffness andenergy loss. Similarly, these TEE-derived indices are predictive of the histopathologicalexpression of aortic collagens and elastin, the balance of which define the passivebiomechanicalbehavioroftheaorticwall.Conclusion: TEE-derived stiffness moduli co-vary with aortic wall biomechanics andhistopathology.Thisanalysisdemonstratesthataddedbenefitusingdynamicimagingoveranaccounted-forchangeinbloodpressure,whichwebelievemayprovideaddedprecisionto better stratify patient populations by mechanical dysfunction, than by simply usingdiameteralone.KeywordsAorta,Biomechanics,Echocardiography,Aneurysms

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#21-BasicScienceMappingof chromosome2differentially expressed aortic genes linkedtovascularinflammationusingcongenicrats

OlgaBerillo1,SofianeOuerd1,Ku-GengHuo1,AsiaRehman1,ChantalRicher3,DanielSinnett3,AnneE.Kwitek4,Pierre Paradis1, Ernesto L. Schiffrin1,2 1Vascular and Hypertension Research Unit, Lady Davis Institute forMedical Research and 2Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGillUniversity, Montréal, QC, Canada, 3Sainte-Justine University Hospital, Montréal, QC, Canada, 4Department ofInternalMedicine,UniversityofIowa,IA,USA

Background:Rat chromosome (RNO) 2 introgression fromnormotensiveBrownNorway(BN) rats intohypertensiveDahl salt sensitive (SS) background (consomic SB2) reducedvascular inflammation. We hypothesized that the BN-RNO2 contains genes that reducevascularinflammation,whichcouldbeidentifiedusingmicroRNA(miRNA)andtotalRNAexpressionprofilinginaortaofcongenicratscontainingdifferentportionsofBN-RNO2ontheSSbackground.Methods: Twelve-to-13-week-old male SS rats and congenic rats containing the distalportionofBN-RNO2(SB2a),themiddlesegment(SB2b)andtheproximalsegment(SB2e)ontheSSbackground, fedanormal-saltdiet,werestudied.Systolicbloodpressure(SBP)wasmeasured by telemetry. Total RNAwas extracted from aorta and used to constructlibrariesforsmallandtotalRNAsequencingusingIlluminaHiSeq-2500.Thebioinformaticspipelineincluded:FastQCforqualitycontrol,STARforgenome(Rattusnorvegicus,release-86)alignment,mirdeep2formiRNAannotationandcounting,Htseq-count formRNAandlongnon-codingRNAannotationandcounting;Rfordifferentialexpressionanalysis.Results: SBPwas lower in SB2a and SB2b but not SB2e compared to SS (125±3, 127±6,138±4vs146±2mmHg,P

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#23-BasicScienceANovelDual-AngleBlade,CorelessVentricularAssistDevice

YoungHoonChung,Dr.RenzoCecere,Dr.RosaireMograin,TouficAzarDepartmentofMechanicalEngineering,McGill University, Montreal, Quebec, Canada Division of Cardiac Surgery, McGill University Health Center,Montreal,Quebec,Canada

Background:Heartfailureisaseriouscardiovasculardiseaseandthemaincauseofdeathintheworld.Thegoldstandardoftreatmentofendstageheartfailureistransplantation.Giventhesevereuniversalshortageofsuitableorgandonors, longtermmechanicalheartsupportservesasanalternativetohearttransplantation.Tothisend,thereisanongoingquest to improve the technology thatwill compete favorablywith heart transplantation.Despite technological advancement, currentpumpdesignspresent important limitations.Conventionalpumpsaredesignedtooperateoptimallyatonespeed,usuallyinapatient’sresting state, and generate high shear stress due to narrow clearance gaps between therotorandthepumpcasingathighspeeds,whichdamagesbloodcells.Methods: Using engineering design methodology and computer simulations, a researchteaminMcGillhassetanobjectiveofovercomingthesechallengesfacedbycurrentpumpdesigns. Novel coreless pump designs were developed and compared to conventionaldesignsbyemployingCFDsimulations.Results: A “Dual-Angle Blade” rotor was initially created to provide optimal flows inmultiple operation points for a conventional rotor. This unprecedented rotor designconsistsoftwosetsofbladeswithtwodifferentangles,eachcorrespondingtoanoptimaloperatingspeed,onasinglehub.Simulationhasshownareductionof20%inoverallwallshearstress incomparison toconventional rotorwithsingleangleblades.By integratingthisadvantagetothecorelessconcept,a“CorelessPump”wasdevelopedtoallowbloodtoflow through its non-obstructed center and provide multiple operating regime. Latestdesign refinements feature magnetic bearing set-up that can house coreless rotor withvarious configurations, such as multiple blade-angles and variable vane thickness andheight. Simulation results have shown an additional improvement upon the previousdesigniteration.Conclusion: We have demonstrated that these novel coreless pump designs reduce theoverallbloodcellshearstressbyminimizingtheblooddeflectionswithinthepumpcasingandcreatingoptimalflowatmultipleoperatingregimesKeywordsVentricularAssistDevice,HearthFailure,CorelessPump

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#24-BasicScienceIdentification of a novel plasma membrane micro-domain interactingwithapolipoproteinA-I

HongChoi,IsabelleRuelandJacquesGenestResearchInstituteoftheMcGillUniversityHealthCentreMontreal,QuebecCANADA

Aims:Thebiogenesisofhigh-densitylipoprotein(HDL)particlesbycholesterol-ladenfoamcells in atherosclerotic lesions is crucial for the removal of excess cholesterol from thelesions. Impairment in the HDL biogenic process contributes to the progression ofatherosclerosis. The aimof this study is to identify novel cellular factors regulatingHDLbiogenesis.Methods and results: HDL biogenesis is a process of apolipoprotein (apo)-mediatedsolubilizationofspecificplasmamembrane(PM)micro-domainsgenerated incholesterolaccumulatedcells.WeestablishedanewmethodtoisolatePMmicro-domainsinteractingwith themajorHDLprotein constituent, apoA-I: apoA-I-cell interactions occurred at 4°Cwere linked using a membrane-impermeable cross-linker, separated from subcellularorganelles using a discontinuous sucrose gradient centrifugation, and purified byperforminganti-apoA-Iimmunoprecipitation.LipidomicandproteomicanalysesofthePMmicro-domainrevealedthatapoA-Ibindstoacholesterol-richPMmicro-domainassociatedwith96proteins.Interestingly,twoPMproteins,caveolinandABCA1wereexcludedfromthe domain, indicating that the apoA-I-associated PMmicro-domains purified under ourexperimentalconditionsaredifferentfrompreviouslyproposedPMdomainsrequiredforHDLbiogenesisasABCA1-createdPMdomainsandcaveolin-containingPMdomainshavebeenknowntocontributetoHDLbiogenesis.Conclusions:Weestablishedanewmethodto isolatePMmicro-domains interactingwithapoA-I. Using thismethod, we found the presence of a novel apoA-I binding PMmicro-domain, suggesting thatapoA-I function inHDLbiogenesismaybe regulatedbymultiplePMfactors.KeywordsAtherosclerosis,Cholesterol,High-densitylipoprotein,Plasmamembranemicro-domains

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#27-ClinicalorPopulationHealthExperiencewith Lomitapide for the treatment of Homozygous familialhypercholesterolemia/TheQuebecExperiencewithLomitapide

SumayahAljenedilMD1,2;ZubinLahijanian1;JeanBergeronMD1;PatrickCoutureMD,PhD4;IsabelleRuelPhD1;JacquesGenestMD1Affiliations:1McGillUniversityHealthCentre;2KingFaisalSpecialistHospital;3UniversitéLaval;4UniversitédeMontréal

Background:HoFHisdefinedasseverehypercholesterolemia(LDL-C>13.0mmol/L)andthepresenceofbi-allelicmutationsinthelow-densitylipoproteinreceptor(LDLR)gene.InQuebec,thereare29knownHoFHsubjects,followedatMcGill,QuebecCityandSaguenay.Patientswith a nullmutationof the LDLRgene require LDL apheresis every twoweeks.Presently,thistechniqueisonlyavailableinQuébecCity.TheMTPinhibitor“Lomitapide”prevents the hepatic formation of apo B lipoproteins and decreases LDL-C byapproximately 50% by an LDL-R independent mechanism. Here, we report the firstexperienceusingLomitapideinfivepatientswithHoFHalreadyonLDLapheresis.Method: This is a retrospective review of five patients with HoFH. The patients werefollowed at 3 lipidology centers in Quebec; McGill University Health Center, Centrehospitalier de l'Université Laval, and Université de Montréal Hospital in Chicoutimi. Allpatientswere treatedwith extracorporeal LDL aphersis everyweek in Qubec city. TheyreceivedLomitapideasanadjunctivetreatmenttotheirconventionaltherapy.Lomitapidewas started at 10 - 20 mg daily and the dose was reduced if not tolerated. LDL-C wasmeasuredpreandpostapheresisandtheaveragewascalculated.Results:Among the5patients,3were initially complaintonLomitapideand theirLDL-Clevelsweresignificantlyreduced(44%intwoand52%inone).Significanttransaminaseselevationinthefirstpatientnormalizedafterreducingthedosefrom20mgto5mgdailyinassociationwithlowfatdiet.Gastrointestinalsymptomsimprovedafterreducingthedosefrom 10 mg daily to 5 mg weekly in the second patient. The third patient had to stoptreatmentdespitegoodtherapeuticresponsebecauseofgastrointestinalsideeffects. Theothertwopatientswerenon-complaintonLomitapidefromthebeginningandhadminimalreduction in their LDL-C (14% and 5%), both eventually discontinued treatmentmainlybecauseoftheintolerablegastrointestinalsymptoms.Conclusion: Our experience of using Lomitapide in HoFH patients was successful inloweringLDL-Clevelsby40-50%.However,themajorityofthepatientsdiscontinuedthetreatment because of the gastrointestinal side effects. Hepatic steatosis needs to beconsideredwithLomitapidetreatment.KeywordsHomozygousfamilialhypercholesterolemia,Lomitapide,Hepaticsteatosis

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#28-ClinicalorPopulationHealthRight ventricular STEMI as a cause of death in idiopathic pulmonaryarterialhypertension

Y. Zhan, B. Burstein, A. Abualsaud, M. Nosair, D. Langleben Center for Pulmonary Vascular Disease, JewishGeneralHospital,McGillUniversity,MontrealQuebecCanada.

Introduction:Thecauseofdeath inadvanced idiopathicpulmonaryarterialhypertension(IPAH) is commonly cardiogenic shock or arrhythmia.Wedescribe a 33 year old femalewith advanced IPAH on IV epoprostenol and oxygen, who had a normal coronaryangiogram12monthspriortoadmission.Shepresentedwithtwodaysofstutteringanginathatbecameconstant.InitialECGshowednewSTElevationinleads1,aVL,V2-V6.RapidCTpulmonary angiogram excluded pulmonary embolism. Urgent cardiac catheterizationshowed discrete obstruction of the first and second acute marginal branches supplyingmost of her right ventricle (RV). Angioplasty and stenting was performed, with partialreperfusion. Echocardiographyshowedaseverelydilatedandhypokineticrightventriclewith no evidence of right to left shunt. She subsequently died of refractory cardiogenicshock before heart-lung transplant could be performed. Right ventricular ischemia is amajorcauseofchestpaininIPAH,andmaycausemyocardialnecrosiswithhightroponins.However,awitnessedrightventricularSTEMI,particularlyinayoungfemale,hasnotbeendescribed.Shedevelopedcoronarylesionswithina12monthperiod,andoneexplanationmightbethathermassiverightventriculardilatationresultedincompressionofheracutemarginals between the RV myocardium and chest wall, with endothelial trauma andthrombus formation. In addition, the dilated right ventricle overlaid thewhole anteriorchestwallexplainingtheECGfindingsonpresentation.Conclusion:AcutemyocardialinfarctionshouldbesuspectedinpatientswithsevereIPAHand ongoing chest discomfort, even without common cardiovascular risk factors. Thedilated right ventricle occupies much of the precordium, making ECG localizationunreliable. Severe right ventricle dilationmight cause coronary compression leading tovascularinjuryandthrombusformation.KeywordsRightventricularST-elevationmyocardialinfarction,Pulmonaryhypertension,Cardiogenicshock

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#30-ClinicalorPopulationHealthRiskStratificationofWPWSyndrome:ADeadlyLow-RiskPathway

MaudePeretz-LarochelleMD1,BarryBursteinMD1,VidalEssebagMDPhD2,3,MartinBernierMD21. McGillUniversity,Montreal,Quebec,Canada2. McGill University Health Centre, Montreal, Quebec, Canada 3. HôpitalSacré-CoeurdeMontréal,Montreal,Quebec,Canada

Background: A 43-year-oldmanwith nomedical history presented after out-of-hospitalcardiac arrest. The initial rhythm was ventricular fibrillation (VF). The patient wasdefibrillated into pre-excited atrial fibrillation (AF), then subsequently underwent directcurrent cardioversion. The electrocardiogram demonstrated sinus rhythm with pre-excitationandnoischemicchanges.Method: The patient underwent electrophysiological study (EPS) which revealed anaccessory pathway (AP) effective refractory period (ERP) of 280ms on and offisoproterenol.With decremental pacing from the atrium the accessory pathway had 1:1atrio-ventricular(AV)conductionat230ms.AFcouldnotbeinduceddespiteburstpacingonandoffisoproterenol.Withisoproterenolinfusionandatrialburstpacingtherewas1:1AVconductionat200ms,reinforcingthehigh-riskpropertiesofthispathway.Thepathwaywassuccessfullyablated.Results: The incidence of VF in patientswith ventricular pre-excitation is approximately1.5%.TherearecurrentlythreeproposedstrategiesforEPSriskstratificationofapatientwithasymptomaticpre-excitation:1)measurementof theshortestR-R interval (SPERRI)during spontaneousor inducedAF; 2)measuring the accessorypathwayERPwith atrialprogrammed extra-stimulation at different cycle lengths; 3) using decremental pacing todefinetheshortestcyclelengthinwhich1:1AVconductionthroughtheAPismaintained.TheSPERRIduringAF is considered thebest indicatorof ahigh-riskpathwaybecause itreproducestheclinicalsituationthatwouldleadonetodevelopVF.TheaccessorypathwayERP is strongly correlatedwith the shortest pre-excited R-R interval (SPERRI) and alsowiththemeanR-RintervalduringAF.Isoproterenolcanbeusedinanattempttounmaskahigh-riskpathway,butdataarelimitedregardingitsabilitytopredictVF.Ourpatientdidnot demonstrate a high-risk pathway ERP with 2 different cycle lengths or withisoproterenol.However,1:1AVconductionovertheAPwithdecrementalpacingat230msdemonstrated high risk properties. The high-risk nature of this pathway was based onextrapolationofSPERRIdata.Conclusion:ThepresentationofthispatientwithVFdemonstratedthehigh-risknatureoftheAP.However,hadthispatientpresentedforroutineEPSwithcurrentguideline-basedriskstratification,whichdoesnotincludedecrementalpacingastoolforriskstratification,thepathwaycouldhavebeenconsideredlowrisk.Thechallengepresentedbythiscaseisthe potential for misclassifying high-risk pathways using the current methods of riskstratification.KeywordsWolff-Parkinson White Syndrome, Cardiac arrest, Electrophysiology study, Riskstratification

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#31-ClinicalorPopulationHealthEarlyLeftVentricularEjectionFractionasaPredictorof SurvivalAfterCardiacArrest

Barry Burstein,MD (Cardiology Fellow,McGill University) Dev Jayaraman,MDMP