Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy
Lakdawala NK, Olivotto I, Day SM, Han L, Ashley EA, Michels M, Ingles J, Semsarian C, Jacoby D, Jefferies JL, Colan SD, Pereira AC, Rossano JW, Wittekind S, Ware JS, Saberi S, Helms AS, Cirino AL, Leinwand LA, Seidman CE, Ho CY. Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy. Circulation Genomic And Precision Medicine 2020, 14: e003062. PMID: 33284039, DOI: 10.1161/circgen.120.003062.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyClinical outcomesNew York Heart Association IIIImplantable cardioverter-defibrillator utilizationSevere heart failure symptomsHeart failure symptomsReduced ejection fractionRetrospective cohort studyImpact of sexSex-based differencesHCM centersCause mortalityTract obstructionBaseline characteristicsCohort studyEjection fractionHeart failureVentricular arrhythmiasFemale sexHCM patientsMyocardial performanceFailure symptomsInternational registrySarcomere variantsHigh burdenMyosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy
Toepfer CN, Garfinkel AC, Venturini G, Wakimoto H, Repetti G, Alamo L, Sharma A, Agarwal R, Ewoldt JF, Cloonan P, Letendre J, Lun M, Olivotto I, Colan S, Ashley E, Jacoby D, Michels M, Redwood CS, Watkins HC, Day SM, Staples JF, Padrón R, Chopra A, Ho CY, Chen CS, Pereira AC, Seidman JG, Seidman CE. Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy. Circulation 2020, 141: 828-842. PMID: 31983222, PMCID: PMC7077965, DOI: 10.1161/circulationaha.119.042339.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsCardiac MyosinsCardiomyopathy, HypertrophicCells, CulturedEnergy MetabolismHumansInduced Pluripotent Stem CellsMiceMolecular Dynamics SimulationMuscle RelaxationMutation, MissenseMyocardial ContractionMyocytes, CardiacMyosin Heavy ChainsProtein ConformationSarcomeresConceptsProportion of myosinAdverse clinical outcomesHypertrophic cardiomyopathyHeart failureUnknown clinical significanceClinical outcomesClinical significancePathogenic variantsSarcomere functionSarcomere protein genesPathogenic missense variantsMyosin missense mutationsHemodynamic requirementsImpaired relaxationContractile abnormalitiesHealthy rodentsHypertrophic remodelingHemodynamic demandsPatient riskPoor relaxationCardiomyocyte contractilityHeart functionMyosin ATPase activityPatientsAllosteric modulators