2021
Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation
Sewanan LR, Park J, Rynkiewicz MJ, Racca AW, Papoutsidakis N, Schwan J, Jacoby DL, Moore JR, Lehman W, Qyang Y, Campbell SG. Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation. The Journal Of General Physiology 2021, 153: e202012640. PMID: 34319370, PMCID: PMC8321830, DOI: 10.1085/jgp.202012640.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyHeart tissueCellular hypertrophyEngineered Heart TissuePathological cardiac hypertrophyThin filament mutationsMavacamten treatmentDiastolic dysfunctionDisease featuresHypertrophic effectCardiac hypertrophyContractile differencesHypertrophyFundamental disease mechanismsCrossbridge activityInherited disorderOverall Ca2Uncertain significancePatient phenotypesDisease mechanismsLow Ca2PatientsK mutationMavacamtenTissue
2019
Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial.
Heitner SB, Jacoby D, Lester SJ, Owens A, Wang A, Zhang D, Lambing J, Lee J, Semigran M, Sehnert AJ. Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial. Annals Of Internal Medicine 2019, 170: 741-748. PMID: 31035291, DOI: 10.7326/m18-3016.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdrenergic beta-AntagonistsAdultAgedBenzylaminesCardiomyopathy, HypertrophicCardiovascular AgentsDose-Response Relationship, DrugDrug Therapy, CombinationExercise ToleranceFemaleHumansMaleMiddle AgedOxygen ConsumptionProspective StudiesStroke VolumeUracilVentricular Function, LeftYoung AdultConceptsObstructive hypertrophic cardiomyopathyLVOT gradientDyspnea scoreAdverse eventsCohort BPeak VO2Hypertrophic cardiomyopathyLeft ventricular outflow tract gradientVentricular outflow tract gradientEnd pointCommon adverse eventsOutflow tract gradientUnrelated adverse eventsOpen-label designPrimary end pointSecondary end pointsPhase 2 trialVentricular ejection fractionML/Peak oxygen consumptionEffect of mavacamtenHigher plasma concentrationsMavacamten treatmentLVOT obstructionTract gradient