2021
Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias
Haghighi K, Gardner G, Vafiadaki E, Kumar M, Green LC, Ma J, Crocker JS, Koch S, Arvanitis DA, Bidwell P, Rubinstein J, van de Leur R, Doevendans PA, Akar FG, Tranter M, Wang HS, Sadayappan S, DeMazumder D, Sanoudou D, Hajjar RJ, Stillitano F, Kranias EG. Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias. Journal Of Personalized Medicine 2021, 11: 502. PMID: 34204946, PMCID: PMC8226909, DOI: 10.3390/jpm11060502.Peer-Reviewed Original ResearchRight ventricleMalignant ventricular arrhythmiasEarly risk factorsAction potential durationCaMKII inhibitor KN93Stress-induced impairmentCellular pathogenic mechanismsProarrhythmic parametersSR Ca loadPrognostic factorsRisk stratificationVentricular arrhythmiasHumanized micePoor prognosisVentricular tachyarrhythmiasFatal arrhythmiasAsymptomatic carriersElectrocardiographic featuresRisk factorsAtrioventricular conductionContractile parametersPotential durationCardiomyopathy onsetPathogenic mechanismsHuman wild type
2018
Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension
Strauss B, Sassi Y, Bueno-Beti C, Ilkan Z, Raad N, Cacheux M, Bisserier M, Turnbull IC, Kohlbrenner E, Hajjar RJ, Hadri L, Akar FG. Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension. Journal Of Molecular And Cellular Cardiology 2018, 127: 20-30. PMID: 30502350, PMCID: PMC6561115, DOI: 10.1016/j.yjmcc.2018.11.017.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAerosolsAnimalsArrhythmias, CardiacConnexin 43Disease Models, AnimalGene Transfer TechniquesGenetic TherapyHeart Conduction SystemHumansMalePotassium ChannelsPulmonary Arterial HypertensionRats, Sprague-DawleyRNA, MessengerSarcoplasmic Reticulum Calcium-Transporting ATPasesTracheaConceptsPulmonary arterial hypertensionSudden cardiac deathVentricular tachyarrhythmiasCTRL heartsExpression of Cx43Conduction velocityArterial hypertensionHeart rateAP durationAdvanced pulmonary arterial hypertensionIncidence of VTOptical action potential mappingPacing-induced ventricular tachyarrhythmiasRisk of VTAEP substrateElectro-mechanical dysfunctionImpaired chronotropic responseMinimal conduction velocitiesRight ventricular failureSustained ventricular tachyarrhythmiasAPD heterogeneityPulmonary vascular remodelingRapid heart rateAge-matched ratsIntra-tracheal delivery
2015
The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus
Xie C, Hu J, Motloch LJ, Karam BS, Akar FG. The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus. Journal Of The American College Of Cardiology 2015, 66: 1144-1156. PMID: 26337994, PMCID: PMC4560843, DOI: 10.1016/j.jacc.2015.06.1329.Peer-Reviewed Original ResearchConceptsAction potential durationVentricular tachyarrhythmiasT2DM heartsIschemia-induced ventricular tachyarrhythmiasOptical action potential mappingType 2 diabetes mellitusAdenosine triphosphate-sensitive potassium channelsMitochondrial adenosine triphosphate-sensitive potassium channelsTriphosphate-sensitive potassium channelsLow-dose diazoxideFree fatty acid levelsIncidence of arrhythmiasNormal Sprague-Dawley ratsSprague-Dawley ratsOnset of arrhythmiasMessenger ribonucleic acid expressionFatty acid levelsRibonucleic acid expressionAPD adaptationElicit arrhythmiasUntreated T2DMIschemic eventsDiabetes mellitusDiabetic patientsIschemic challenge
2008
Arrhythmia Mechanisms in the Failing Heart
JIN H, LYON AR, AKAR FG. Arrhythmia Mechanisms in the Failing Heart. Pacing And Clinical Electrophysiology 2008, 31: 1048-1056. PMID: 18684263, DOI: 10.1111/j.1540-8159.2008.01134.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHeart failureArrhythmia mechanismsFundamental arrhythmia mechanismsSudden cardiac deathLethal ventricular tachyarrhythmiasCalcium handling proteinsEffective treatment strategiesCardiac deathMalignant arrhythmiasVentricular tachyarrhythmiasElectrical remodelingConduction abnormalitiesFailing HeartTreatment strategiesLethal arrhythmiasElectrophysiological substrateHandling proteinsAction potentialsPatientsArrhythmiasIon channelsDeathHeartTachyarrhythmiasAbnormalities
2005
Conduction Abnormalities in Nonischemic Dilated Cardiomyopathy: Basic Mechanisms and Arrhythmic Consequences
Akar FG, Tomaselli GF. Conduction Abnormalities in Nonischemic Dilated Cardiomyopathy: Basic Mechanisms and Arrhythmic Consequences. Trends In Cardiovascular Medicine 2005, 15: 259-264. PMID: 16226681, DOI: 10.1016/j.tcm.2005.08.002.Peer-Reviewed Original ResearchConceptsConduction abnormalitiesVentricular dysfunctionHeart failureMolecular mechanismsLeft ventricular dysfunctionNonischemic heart failureIschemic heart diseaseExtracellular matrixGenesis of arrhythmiasMyocyte excitabilityMechanistic differencesOrgan levelMembrane excitabilityVentricular tachyarrhythmiasDisease etiologyMyocardial infarctionHeart diseaseArrhythmogenic substrateSudden deathArrhythmic consequencesCell couplingAbnormalitiesBasic mechanismsDysfunctionExcitabilityIon channels as novel therapeutic targets in heart failure
Akar FG, Tomaselli GF. Ion channels as novel therapeutic targets in heart failure. Annals Of Medicine 2005, 37: 44-54. PMID: 15902846, DOI: 10.1080/07853890510007214.Peer-Reviewed Original ResearchConceptsHeart failureIon channel functionAnti-arrhythmic therapyLethal ventricular tachyarrhythmiasCalcium handling proteinsNovel therapeutic targetPublic health epidemicIon channel dysfunctionChannel functionVentricular tachyarrhythmiasTherapeutic targetChannel dysfunctionHandling proteinsSodium currentHealth epidemicNovel targetImpulse generationElectrical phenotypeIon channelsCurrent understandingTachyarrhythmiasFailureDysfunctionTherapyAbnormalities
2003
Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure
Akar FG, Rosenbaum DS. Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure. Circulation Research 2003, 93: 638-645. PMID: 12933704, DOI: 10.1161/01.res.0000092248.59479.ae.Peer-Reviewed Original ResearchConceptsPolymorphic ventricular tachycardiaHeart failureQT interval prolongationQT intervalM cellsConduction blockAPD prolongationTransmural wallAction potential duration prolongationRapid ventricular pacingTransmural heterogeneityFunctional conduction blockVentricular tachyarrhythmiasPremature impulsesSubepicardial zoneVentricular pacingVentricular tachycardiaHF phenotypesDuration prolongationCanine wedge preparationSelective prolongationDecremental conductionAction potentialsOptical action potentialsVentricular wall